Biomolecular Applications
for bioMEMS
Biomolecular Applications PK
Activities (3)
Participant Guide
www.scme-nm.org
Biomolecular Applications for bioMEMS
Primary Knowledge
Participant Guide
Description and Estimated Time to Complete
This unit discusses the characteristics and phenomena of biomolecules that make them attractive
components for bioMEMS devices. It provides information that helps you understand how
biological molecules can be used as working devices within bioMEMS.
Estimated Time to Complete
Allow at least 30 minutes to complete.
Introduction
A MEMS cantilever coated with a monolayer of biological molecules (probe surface layer) can bind
with and capture other molecules (analytes) of complementary shapes
As MEMS devices become smaller and smaller, the use of biomolecules as a MEMS component
becomes more attractive. But how can biomolecules be used as a MEMS component?
 Biomolecules can self-assemble into predictable and precise structures in the nano range. This
offers a vast new repertoire of structures and functions to MEMS devices.
 Many of these molecules’ functions in living organisms can be harnessed to perform the same
functions in a bioMEMS device. This provides a wealth of materials and applications that can
be applied to bioMEMS design.
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To understand how biomolecules can be used in bioMEMS, it is useful to learn about the types of
biomolecules and how they associate with each other in functional units. The following information
gives a brief overview of the possible applications of biological molecules in the design of
bioMEMS. It describes some of the properties that make biological molecules assemble and
function.
Objectives
The objectives of this section are
 State the types of biological structures that are useful in bioMEMS.
 Describe at least three (3) types of functions that biological structures can provide in bioMEMS
design.
 State at least two (2) size dimensions of biological structures used in bioMEMS.
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Key Terms (Definitions of key terms are in the glossary at the end of this unit)
Analyte
Antibody
Antigen
Biosensor
Cantilever
Cell surface receptor
Collagen
Complementary DNA sequence
DNA hybridization
Drug delivery
Enzyme
Flagella
Gene technology
Hydrogen bonding
Hydrophilic effect
Hydrophobic effect
Lab-on-a-chip devices
Ligand
Liposome
Macromolecule
Microfilament
Microtubule
Nanoparticles
Nucleotides
Organelle
Oxidation
Phospholipid
Protein
Reduction
Scaffold
Self-assembly
Solvent
Supramolecular structure
Vesicles
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What are biomolecules?
Biomolecules – DNA and Proteins
[Image source: Swiss Institute of Bioinformatics (SIB) gallery]
A molecule is the smallest form of a substance that contains all the properties of that substance. A
molecule is made from atoms. For example, a single H2O molecule is the smallest form of water.
You break it up and you have two atoms of hydrogen and one atom of oxygen.
Biomolecules are the molecules of life. All known forms of life are comprised solely of
biomolecules. Biomolecules are formed by the self-assembly of atoms (primarily carbon and
hydrogen). Once formed, biomolecules continue to self-assembly into larger structures such as
larger molecules, compounds, organelles and cells. It is the structure, the three-dimensional shape
and the conformation that determines the role a biomolecule plays in the complex chemical
processes of life.
There are four types of biomolecules that are abundant in all cells: carbohydrates, nucleic acids,
proteins and lipids.
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Biomolecule
Carbohydrates
Nucleic Acids
Proteins
Lipids (fats and oils)
Types and functions of biomolecules
Carbohydrates have both structural and energy storage abilities.
Monosaccharides (simple sugars such as glucose)
Disaccharides (lactose, maltose and sucrose)
Polysaccharides (cellulose, glycogen, and starch)
DNA (The main constituent of genes. DNA passes hereditary
characteristics from one generation to the next.)
RNA (Triggers the manufacture of specific proteins. Involved in
the transmission of DNA's genetic information.)
Enzymes (Catalyze or accelerate cellular reactions)
Collagen, keratin, and elastin (Structural or support proteins)
Hemoglobin (Transport proteins)
Casein, ovalbumin (Nutrient proteins)
Antibodies (Necessary for immunity)
Hormones (Regulate metabolism)
Actin and myosin (Perform mechanical functions such as muscle
contraction)
Triglycerides (A form of stored energy)
Phospholipids (The major components of the biological cell
membrane. Able to limit the passage of water and other watersoluble compounds through the membrane.)
Table 1: Types of Biological Molecules
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Biomolecules in MEMS Devices
Nanocantilevers coated with antibodies that capture viruses (red spheres)
[Image generated and printed with permission by Seyet, LLC]
Biomolecules offer bioMEMS engineers a multitude of structures and functional applications.
These molecules come in all sizes and shapes within the nano-size range of dimensions.
Biomolecules assemble themselves from solutions into biomolecular structures. Their designs
have evolved to perform quite specific tasks; tasks which can be applied to a bioMEMS function.
Here are examples of some of these tasks and functions:




Biomolecules have the ability to specifically recognize and bind to a particular molecule in a
complex solution. This can be applied to a biosensor function.
Some enzyme-catalyzed (accelerated) reactions can be used as a biosensor where the catalyzed
reaction is detected rather than the binding process itself.
Some enzyme-catalyzed reactions are used by living cells to generate energy from small
molecules that are readily available in body fluids. These same enzymes can be used in
implantable devices to replace the need for batteries.
Other proteins are used by cells to move particles about within the cell, or to move the cell itself
around in its environment. These same proteins can be used as actuators in a bioMEMS device.
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Biomolecules used in bioMEMS
Three types of biomolecules are being used and studied for bioMEMS interfaces:



Nucleic acids, such as DNA - These are the molecules that
cells use to carry genetic information.
Proteins, such as enzymes, fibers, molecular motors,
channels and pores, vesicles - These molecules are often
referred to as the "work horses" of the cell because they
perform so many of the jobs of cellular metabolism.
Lipids, such as phospholipid vesicles and membranes These are relatively small molecules that self-assemble into
very thin membranes in order to make separate
compartments in the cell. They also provide a membrane
barrier on the outside of all cells.
What will you explore in this unit?
Double-stranded DNA molecule (a
nucleic acid)
In the following discussion,
 You will explore how nucleic acids, proteins, and lipids self-assemble into structures that have a
functional application in bioMEMS devices.
 You will discover how some of the functions of biomolecules provide the specific recognition
properties required in a biosensor-type application.
 You will explore some interesting applications of biomolecules based on their structure
 You will see how some biological molecular motors move within the nanoscale.
Biomolecular Self-Assembly
A unique property of biological molecules is the ability to recognize each others’ molecular surfaces
in order to bind and assemble into a complex structure. This ability to self-assemble is like having a
3-dimensional jigsaw puzzle solve itself. Each
piece would find its own nearest neighbors from
all the other pieces, assemble, and then continue
until the entire puzzle is solved. This amazing
process of self-assembly relies on the
continuous motion of molecules in a solution
and the resulting collisions. The molecules
collide with each other until they encounter
molecules to which they can bind. Their unique
shape and surface chemistry define how they
assemble in solution. This complex process is
what takes place when you perform the simple
task of blowing a bubble.
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DNA Self-Assembly
Double-stranded DNA
A DNA molecule is a double-stranded helix. Sugar and phosphate groups for the ladder.
Nucleotide bases form the steps of the ladder. DNA self-assembly is when two single strands of
DNA assemble into a double helix (see graphic of Double-stranded DNA). This occurs if the
nucleotide bases in each strand of DNA have complementary sequences where the bases pair off
with the correct hydrogen bond between them. The cumulative effect of large numbers of hydrogen
bonds in a long DNA molecule stabilizes the double helical structure. Only high temperatures can
overcome the hydrogen bonding and split the double helix into separate strands. (For more
information on DNA and DNA replication, read SCME's DNA Overview)
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In a type of biosensor (see above graphic) that contains
genetic information, a single strand of DNA can "capture"
or detect its complementary strand of DNA (the "target").
This selective binding of a molecule is the basis of DNA
microarrays, or gene chips. The binding of target DNA can
be detected in many ways, depending on the technique used
in the MEMS design. .
There are many applications of DNA microarrays in
medicine. DNA microarrays can be used to detect
infectious agents or genetic disease. Applications in public
health include detection of contamination in food and
water.
A DNA molecule of a specific sequence (“target DNA”) can
be detected on a DNA microarray by binding to a singlestranded DNA strand (“probe”) that has a sequence that is
complementary to it.
Protein Self-Assembly
Ribbon diagrams of quaternary protein structures
[Image source: Research Collaboratory for Structural Bioinformatics Protein Data Bank]
Similar to DNA self-assembly, certain proteins will associate with other specific proteins that
complement the shape and chemistry of their surfaces. This causes proteins to coordinate with each
other in what is referred to as quaternary protein structures (see figure).
These protein structures assemble into superstructures using an instruction manual that has become
internally "hardwired" through the evolution of cells and organisms. Inside the cells, newly
assembled proteins in the cytoplasm are constantly moving, vibrating, rotating, and gliding in
solution, bouncing off each other like dancers in a discotheque. When a protein happens to bump
into a "partner" protein that has a complementary surface shape and chemistry , the two subunits
"plug into" each other and continue their dancing motion as a functional pair. This continues until
all the protein subunits have been found and assembled into the final functional structure. At that
point, the work of self-assembly is finished.
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Example of Protein Self-Assembly
Microtubule
[Image Courtesy of Lawrence Berkeley National Laboratory]
This image show a microtubule, a principal component of the cell's skeleton. This microtubule is
formed by the self-assembly of tubulin dimers (a type of protein molecule). Each tubulin dimer
binds to other tubulin dimers in order to "grow" this large spiral microtubule. The association of
hundreds to thousands of tubulin dimers into a long microtubule spiral then into a microtubule is an
example of a supramolecular structure. Keep in mind that this microtubule is a nanostructure,
approximately 20 - 30 nanometers in diameter.
Applications of Biomolecular Self-Assembly
Because of their size, biomolecules provide a convenient means to further miniaturize MEMS
devices. The highly predictable and unique nanoscale structures created by biomolecules range in
size from sub-nanometer to micrometer, and in some cases millimeter, depending on the type of
biomolecule.
The ability of biomolecules to self-assemble provides a faster, cheaper, and more reliable means of
generating a 2-dimensional pattern or a 3-dimensional architecture on a bioMEMS surface. The
structures formed through self-assembly can be used as templates or scaffolding for deposition of
other organic or inorganic molecules. Such supramolecular structures form useful nanoscale
particles or fibers such as nanowires or nanotubes.
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A Biomolecular Filter
AFM image of bacterial cell S-layer proteins (Scan size 250 nm x 250 nm)
[Agilent Technologies. Image Courtesy of T.Hopson]
Crystalline bacterial cell surface layer (S-layer) proteins (see figure) are building blocks of one of the
simplest self-assembly systems. S-layer proteins form the outer most cell envelope of bacteria by building a
monolayer lattice generally 5 – 10 nm thick. . These monolayers find analytical application through their
ability to separate and identify molecules, thus acting as a filter. Such nanofilters offer new approaches to
water purification and environmental cleanup.
The Function of Cell Surface Receptors
Proteins play many roles in the cell.
One role is as a cell surface receptor:
A protein embedded in the plasma
membrane of a cell is directly
concerned with cell communications
(getting information from outside the
cell to the inside of the cell). The
information transferred comes from
signal molecules. This cell surface
receptor protein has a very
hydrophobic site to anchor itself into a
surface membrane. It has another site
for binding to a signal molecule. The signal molecule
binding site has the exact shape and chemistry
required for binding to a specific protein. This
binding is referred to as a lock and key model, where
the protein is the lock that fits one exact key. Only a
signal molecule of the correct shape and position will
bind and become "locked to" the protein. All other
molecules are rejected as "imposters".3
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Cell Surface Receptor – Transfers the
information from a protein outside the
cell, to the interior of the cell.
[Image courtesy of "The Science Creative
Quarterly" (scq.ubc.ca). Illustrator:
Jane Wang]
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The Function of Enzymes
Like receptor proteins, enzymes can also recognize specific molecules and bind to them. Like a cell
surface receptor, an enzyme active site has a shape and surface chemistry that allows for recognition
and binding of specific or complementary molecules. The binding process is through multiple weak
intermolecular interactions (such as hydrogen bonds).
Unlike cell surface receptors, once a target molecule binds to a capture molecule on the enzyme
active site, the enzyme catalyzes a chemical reaction to form products that leave the enzyme. This
leaves the active site open to catalyze reactions again and again between target and capture
molecules. Enzyme active sites generate a "signal" as a result of the binding of molecules and the
catalyzed reactions. This signal is monitored in enzyme biosensors.
Enzymes as Biosensors
An example of an enzyme biosensor is the glucose
monitor (see graphic – Glucose monitor). The glucose
monitor is the most common diagnostic bioMEMS on
the market.10 It uses the enzyme "glucose oxidase"
from a blood sample (red dot) to recognize and
transform glucose molecules. Glucose molecules are
oxidized to gluconolactone molecules, releasing
electrons (e-) that can be detected at an electrode.
Glucose Monitor (biosensor)
Energy Generation by Enzymes
Another attractive property of certain enzymes for bioMEMS applications is their ability to generate
energy in response to an environmental change. For example, an enzyme called ATP synthase
responds to a change in pH on one side of a membrane, generating ATP (adenosine triphosphate) on
the other side of the membrane. The generation of ATP molecules is important in that these
molecules transport the chemical energy within cells that is used for metabolism. There are other
enzymes that convert the energy of high-energy molecules into ATP. For bioMEMS, this energyproducing property of enzymes can be useful in replacing the bulky battery packs of implantable
devices.
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MEMS Biosensors
This ability of a cell surface receptor to
recognize an exact molecule in chemically
complex body fluids can be simulated in a
MEMS biosensor. In the biosensor in the
graphic to the right, the surfaces of the
sensors (cantilevers) are coated with the
"capture" molecule. A capture molecule
binds to a "target" molecule. When a
target molecule binds to a capture
molecule, a bioMEMS device detects the
binding and sends a signal to a detector.
The Function of Antibodies
Nanocantilevers coated with antibodies that capture viruses (red spheres)
[Image generated by Seyet, LLC]
Antibodies are proteins made and secreted by immune cells. Antibodies bind to specific molecules
that are foreign to the body. In laboratory research, these foreign molecules, called antigens, are
used to induce an immune reaction in a laboratory animal. Once the animal becomes "immunized"
by antigen injections, antibodies are secreted by the animal's immune cells. Those antibodies that
recognize the injected antigen are isolated from the animal’s blood. Monoclonal antibodies are
identical antibodies that are produced by one type of immune cell. This immune cell and its clones
can be isolated and extracted from the lab animal. Using this process a bioMEMS engineer can
generate cell cultures that produce monoclonal antibodies that bind to specific target molecules.
A common application of monoclonal antibodies in bioMEMS devices are protein microarrays (see
graphic). Similar to the process of DNA microarrays, protein microarrays use thousands of
different monoclonal antibody "capture" molecules as the surface of a biosensor. When a capture
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molecule binds with a target molecule, the chemical reaction that takes place is detected.
This graphic illustrates the function of a protein microarray. This microarray consists of
nanocantilevers coated with a monolayer of antibodies to be used as the "capture" molecules. The
"target" molecules are viruses. Notice how "target" molecules (red spheres) bind to the antibodies
on the surface of the cantilever. Such an array could also have a different antibody monolayer on
each nanocantilever. This would allow the capture of different target molecules within the same
solution or sample.
Future medical application of a protein arrays include the following:
 A diagnostic for diseases that create an imbalance in proteins found in cells or body fluids.
 A protein array coupled to a drug delivery device could target a specific cell type. For example,
an antibody that recognizes a cancer antigen can be used to seek out and target cancer cells.
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The Function of Phospholipids
Phospholipid and Bilayer Membrane
Phospholipids are very small lipid molecules that are a major component of all biological
membranes. Phospholipids self-assemble into membranes, mainly through hydrophobic and
hydrophilic interactions. The graphic above shows a phospholipid with its hydrophobic tail and
hydrophilic head. To form a bilayer membrane, the hydrophobic tails associate with each other and
the hydrophilic heads line up together on either side of the membrane. The graphic on the right
shows a bilayer membrane (the hydrophilic heads in green and the hydrophobic tails in black).
This membrane serves as a very thin, but very effective barrier. Polar or charged molecules cannot
cross a phospholipid membrane. These bilayer membranes, in combination with membrane
proteins, form the natural barriers surrounding all living cells, providing a structural and barrier
function.
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The Liposome Drug Delivery System
Lipsome (red) with drug (blue) in cavity
This graphic shows a liposome (a spherical vesicle composed of a phospholipid bilayer membrane
with an aqueous solution in the core). Can you identify the phospholipid heads and tails in this
graphic?
In bioMEMS design liposomes are being used for drug delivery systems. The bilayer membrane
can sequester drugs within the liposome core (drugs shown in blue). The drug carrying liposomes
can be injected into the bloodstream where they are carried to the target area (such as a tumor). The
proteins in the membrane utilize the "lock and key" process to lock on to a target molecule
(cancerous tumor cell). The liposome fuses to the membrane of the target molecule. The drug
inside the liposome slowly travels through the membrane and into the cancerous cell (like a timedrelease capsule).
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The Function of Porin Proteins
(Left) Ribbon diagram of a porin. (Right) Top view of the same porin molecule in a ribbon diagram
(top) and atomic detail (bottom). Notice the pore through the middle of the structure.
[Image source: Tulane University, BioChemistry/ RCSB Protein Databank]
Porin proteins are a class of outer membrane proteins found in bacteria. Porins are barrel proteins
which cross a cell's membrane and act as "nanopores" through which molecules can diffuse. These
nanopores act as channels which are specific to different types of molecules.
In bioMEMS design, nanopores are being studied and engineered for various applications:
 Molecule separation - To separate molecules based on size, charge, and hydrophobicity
 "Gating" channels– To control when a molecule is allowed to pass through the membrane.
 Analyte detection – To selectively bind with specific analytes passing through the nanopore,
thereby partially blocking the channel. By measuring the conductance of ions through channel,
analyte concentration can be directly detected.
The Function of Molecular Motors
Strictly speaking, all cellular receptors and enzymes are molecular machines because they all have
moving parts. Internal movement within protein and enzymes occurs when the capture molecules
bind with the target molecules. This binding process results in a change in shape or re-arrangement
of the atoms that make up the protein. The range of motion of this rearrangement is generally very
small and subtle, on the order of nanometers. However, the movement is large enough to be
detected with the right microsensor.
In contrast, relatively large movements are produced by protein molecules or "motors" within cells.
One function of a protein motor is to move "cargo" around in the cell. Other protein motors are
responsible for providing locomotion for the cell, or for transporting particles within the cell. Some
of these motors have a linear motion, while others have a rotary motion. In bioMEMS devices, such
motors can be used for similar functions as their macroequivalents.
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Linear Motion Molecular Motors
Molecular motors that have linear motion move along microtubules or microfilaments within the
cell. Three such motors are the kinesin, dynein, and the myosin protein molecules. They all
transport cargo that includes other proteins, membrane vesicles and organelles.
Kinesin and Dynein Linear motors
Kinesin and Dynein Protein Molecules (Molecular linear motors)
Kinesin and Dynein (shown in the figure above) are protein molecules that exist in the living cells of
all plants and animals. These molecules can "walk" along tube-like material called microtubules.
They crawl "hand-over-hand", using two "heads" like feet to move forward. This action allows
these molecules to transport material within cells. Kinesin proteins travel toward the positive end of
the microtubule while dynein proteins travel toward the negative end. Some viruses such as herpes
and smallpox use kinesin molecules to move within an infected cell.
Myosin Linear Motor
Another linear motor is myosin protein, which travels along a
microfilament in muscle cells causing muscle contraction. The figure
shows a myosin (green) "walking" in nanosize steps along a microfilament
(red). As the myosin molecule walks it pulls on the microfilament causing
the muscle cells to contract.
Myosin Protein Molecule (A molecular linear motor)
[Illustration by PrecisionGraphics.com. Printed with permission by the
University of Illinois]
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Bacterial Flagellar Rotary Motor
Bacterium Cell (left) and Bacterial Flagellar Motor (right)
[Graphics courtesy of Mariana Ruiz Villarreal]
Two types of molecular rotary motors are the bacterial flagellar motor and the enzyme ATP
synthase.
The bacterial flagellar motor is responsible for the locomotion of bacterial cells. A flagellum is a
long, slender tail or tube that projects from a bacterium cell (see figure-left). The detail in the right
figure illustrates the flagellum as an assemblage of rotor, stator and filament. A bacterium can have
several flagella. The concentrated whip-like motion of the filaments causes the rotors to turn. This
propels the bacterium through its medium.
The ATP synthase rotary motor
The ATP synthase motor is an enzyme embedded in a
cell membrane. This enzyme is responsible for
generating ATP (adenosine triphosphate), a high-energy
molecule that is the universal fuel of cells.. As the ATP
synthase motor spins, ATP is created.
The ATP synthase motor (see figure) is powered by
incoming protons (H+) that cause a difference in electrochemical potential to occur across its rotor membrane (as
illustrated in the figure). The energy from this potential
difference is transduced to mechanical energy which
spins the motor. As the motor spins, ATP is generated
by the rotor inside the cell.
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Other molecular motors use this ATP as fuel. For example, each molecule of ATP that a linear
motion kinesin motor encounters triggers precisely one, 8 nm step along its microtubule.
All of these molecular motors enable MEMS engineers to integrate the functions of macromotors
into micro and nanoscale devices.
Food For Thought
1. What types of biomolecules are being investigated for use in bioMEMS designs?
2. How can the specific types of structures and functions of biomolecules be used to do the work in
bioMEMS designs?
3. On what scale are the sizes of the biomolecules being used in bioMEMS?
Summary



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Biomolecules have precise recognition properties that can provide self-assembling structures for
bioMEMS surfaces. This property is also useful for biosensing and separations in bioMEMS
design.
The use of simple biological subunits that can assemble in complex 3-D structures provides a
simpler, faster, and less expensive route to nanoscale structures than do most top-down types of
fabrication. Useful 3-D structures include channels and pores that can discriminate according to
size or chemical properties, providing a means for chemical separations.
The active site recognition of enzymes and other binding proteins can discriminate between
small differences at the atomic scale. This is very useful in biosensor designs.
DNA microarrays can be used to capture or detect complementary strands of DNA. These
microarrays can be used in a biosensor for analyzing genetic information.
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Summary Table
The following table summarizes types of biomolecules and their function in bioMEMS devices.
Biomolecule
Example
Nucleic
acids
DNA
Proteins
Receptors and Biosensing an analyte by
antibodies
capture (binding) to a target
molecule (analyte)
Protein microarrays
Enzymes
Biosensing an analyte by
catalyzing a specific
chemical reaction
Monitoring blood glucose levels
with glucose oxidase
Channels &
pores
Separation of molecules by
size
Membrane embedded with
bacterial porin proteins for
molecular separations by size
differences
Molecular
motors
Moving particles
Actuators
Filters
Identify and separate
molecules
Nanofilters for water purification
Lipids
Function in a bioMEMS
device
Recognition of a DNA
sequence by selective
binding sites
Phospholipids Sequester solutions into
membrane-coated
compartments
An example of an application
DNA microarrays
Storage compartments for drug
delivery devices
Table 2: Biomolecules and their functions in bioMEMS devices
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References
1.
"BioMEMS: State-of-the-art in Detection, Opportunities and Prospects." Bashir, R.
Advanced Drug Delivery Reviews (2004)
https://engineering.purdue.edu/LIBNA/pdf/publications/BioMEMS%20review%20ADDR%
20final.pdf
2.
Biomolecules: DNA and Proteins Image: Swiss Institute of Bioinformatics (SIC).
Publication: Gasteiger E., Gattiker A., Hoogland C., Ivanyi I., Appel R.D., Bairoch A.
ExPASy: the Proteomics server for in-depth protein knowledge and analysis Nucleic Acids
Res. 31:3784-3788(2003).
3.
"Cell Surface Receptors: A Biological Conduit for Information Transfer". David Secko.
The Science Creative Quarterly. Issue 3. http://www.scq.ubc.ca/cell-surface-receptors-abiological-conduit-for-information-transfer/
4.
"Molecular Motors". Bates, Karl Leif. Michigan Today. University of Michigan. 2004.
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Nano Letters. 6:2121-2129 (2006)
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"Toward intelligent molecular machines: directed motions of biological and artificial
molecules and assemblies." Kinbara, K. & T. Aida. Chem. Rev. 105:1377-1400. (2005)
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"Nanostructuring by deposition of protein channels formed on carbon surfaces." Niederweis,
M, C. Heinz, K. Janik & S.H. Bossmann. Nano Letters. 2:1263-1268 (2002)
9.
Nanobiotechnology: Concepts, Applications and Perspectives. Niemeyer, C.M. & C.A.
Mirkin (Eds). Wiley-VCH (2005)
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Fundamentals of BioMEMS and Medical Microdevices. Saliterman, S.S. Wiley-Interscience.
(2005)
11.
"Patterned assembly of genetically modified viral nanotemplates via nucleic acid
hybridization." Yi, H., S. Nisar, S-Y. Lee, M.A. Powers, W.E. Bentley, G.F. Payne, R.
Ghodssi, G.W. Rubloff, M.T. Harris, & J.N. Culver. Nano Letters. 5:1931-1936. (2005)
12.
"Fabrication of novel biomaterials through molecular self-assembly." Zhang, S. Nat.
Biotech. 21:1171-1178. (2003)
13.
"Third-generation biosensors based on the direct electron transfer of proteins." Zhang, W. &
G. Li. Anal. Sci. 20:603-609. (2004)
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Biomolecular Applications for bioMEMS PK
14.
15.
16.
17.
Biotechnology glossary
http://biotechterms.org/sourcebook/savegotcategory.php3?firstchar=A
nanotechnology glossary
http://www.discovernano.northwestern.edu/whatis/whatis/Glossary
(sources of graphics & movies not listed here)
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Glossary
Actin microfilament -- A 2-stranded helical polymer of the protein actin that form the thin
filaments of muscle and the cytoskeleton of cells where they are highly concentrated just below
the plasma membrane.
Amphipathic -- Describing a molecule, such as a phospholipid, that contains both hydrophobic
(i.e. nonpolar) and hydrophilic (i.e. polar) parts.
Analyte -- A component to be measured in an assay or test.
Antibody -- A protein that is capable of binding noncovalently, reversibly, and in a specific
manner with a corresponding antigen. They are produced in higher animals by cells of the
immune system in direct response to the introduction of immunogens (antigens), and circulate in
the blood.
Antigen -- Any agent that, when introduced into an immunocompetent animal, stimulates the
production of a specific antibody or antibodies that can bind to the antigen.
ATP synthase - A general term for an enzyme that can synthesize adenosine triphosphate (ATP)
from adenosine diphosphate (ADP) and inorganic phosphate by utilizing some form of energy.
Biosensor – A sensor that can detect specific biological compounds present in a gas or liquid.
Receptor biomolecules, such as antibodies, are attached to a sensor device that can detect a
mechanical change (such as an increased mass on a cantilever), a change in conductivity (such
as an enzyme that carries out a oxidation or reduction reaction), or an optical change (such as an
analyte that carries a fluorescent molecule tag).
Cell surface receptor -- A protein embedded in the plasma membrane of a cell that undergoes
binding with a hormone, neurotransmitter, drug, or intracellular messenger molecule to initiate a
change in cell function. Receptors are concerned directly and specifically with cell
communications that involve signal molecules.
Collagen -- A group of fibrous proteins of very high tensile strength that form the main
component of connective tissue in animals.
Complementary DNA sequence -- Sequence of nucleotide bases that are complementary to
each other, forming the hydrogen bonds of base pairs in a double helix.
Cytoskeletal elements – Filamentous proteins within the cytoplasm of cells that provide
structural stability of cell shape and have roles in cellular movement and movement of particles
through the cytoplasm. Includes intermediate filaments, microfilaments, and microtubules.
DNA hybridization -- The process of forming a hybrid DNA double strand between singlestranded DNA polymers that have sequences that are complementary to each other, allowing
formation of the hydrogen bonding of complementary base pairs.
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Drug delivery - The use of physical, chemical, and biological components to deliver controlled
amounts of a therapeutic agent.
Enzyme – A macromolecular substance composed wholly or largely of protein, that catalyzes
one specific biochemical reactions. The substances upon which they act are known as
substrates, for which the enzyme possesses a specific binding or active site.
Enzyme substrate – The molecule that binds to an enzyme active site under catalysis of a
chemical transformation.
Flagella -- (singular, flagellum) A fibrous protein assembly that forms the specialized
locomotive appendage of bacteria. It is commonly 3-20 um long and 12-25 nm in diameter, is
built up of several (often 3) longitudinally arranged chains of flagellum protein subunits, often
assembled in a long spiral. A basal body anchors it to the cell envelope, where a flagellum
motor molecule imparts rotary motion to it.
Gene technology - Techniques that allow experimenters to manipulate specific genes within an
organism and determine the effect this has on the functioning of the organism.
Hydrogen bonding - The interaction of a hydrogen atom with another atom, influencing the
physical properties and three-dimensional structure of a chemical substance. Hydrogen bonding
generally occurs between atoms of hydrogen and nitrogen, oxygen, or fluorine. An important
example of a hydrogen bonding is the formation of the DNA double helix.
Hydrophilic effect -- Having an affinity for, attracting, adsorbing, or absorbing water.
Hydrophilic effect occurs when a liquid comes in contact with another phase — typically a solid
substrate that attracts the liquid molecules — causing the liquid to attain a relatively large
contact area with the substrate.
Hydrophobic effect -- Lacking an affinity for, repelling, or failing to adsorb or absorb water.
Hydrophobic effect occurs when a liquid comes in contact with another phase — typically a
solid substrate, that exerts a repulsive force onto the liquid — causing the liquid to retract from
the surface, with relatively little contact area between liquid and substrate.
Intermediate filament -- A type of protein filament that contributes to the cytoskeleton of cells.
Composed of heterogeneous subunit proteins, they are involved in mechanically integrating the
cytoplasm of the cell with the cell membrane.
Ion channel - A protein-coated pore in a cell membrane that selectively regulates the diffusion of
ions into and out of the cell, allowing only certain ion species to pass through the membrane.
Lab-on-a-chip (LOC) devices - Miniaturized analytical systems that integrate a chemical
laboratory on a chip. Lab-on-a-chip technology enables portable devices for point-of-care (or onsite) medical diagnostics and environmental monitoring.
Ligand -- A molecule that is bound selectively to one or more specific sites on another
molecule (as in the combination of antigen with antibody, of hormone with receptor protein, of
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enzyme substrate with enzyme active site, etc)
Liposome - A type of nanoparticle made from fat molecules surrounding a core of water.
Liposomes were the first nanoparticles used to create unique therapeutic agents.
Microfilament -- A type of actin filament that contributes to the cytoskeleton of cells. The
major component of a cell’s contractile machinery, used for cell movement and muscle
contraction.
Macromolecule - A very large molecule composed of hundreds or thousands of atoms, built
from connecting a large number of simple subunits such as nucleotide (for nucleic acids) or
amino acids (for proteins).
Microtubule -- A long, generally straight, narrow protein filament consisting of a
supramolecular structure of tubulin proteins arranged in a helical pattern. Microtubules exist in
equilibrium with a pool of tubulin monomers in the cell cytoplasm and can be rapidly assembled
and disassembled in response to various physiological stimuli. They play a role in the cell
cytoskeleton, providing a tract for motor proteins to move cargo around the cell.
Monomer - A small molecule that may become chemically bonded to other monomers to form a
polymer; from Greek mono "one" and meros "part". The subunits used to make polymers or
macromolecules.
Nanoparticles - Particles ranging from 1 to 100 nanometers in diameter. Semiconductor
nanoparticles up to 20 nanometers in diameter.
Noncovalent interactions - Interactions first recognized by J. D. van der Waals in the nineteenth
century. In contrast to the covalent interactions, noncovalent interactions are weak interactions
that bind together different kinds of building blocks into supramolecular entities. Also referred
to as van der Waals interactions.
Nucleotides -- Building blocks used to make nucleic acids (DNA, RNA). There are 4
nucleotide bases found in the synthesis of DNA (guanine, cytosine, adenine, and thymine) and 4
nucleotide bases found in the synthesis of RNA (guanine, cytosine, adenine, and uracil).
Oxidation - Chemical reaction in which a molecule loses one or more electrons to another
component of the process.
Phospholipid -- Any lipid comprised of a glycerol bound to a phosphate group and two fatty
acids by ester bonding. The phosphate group can have various charged or polar groups attached,
while the fatty acids can vary in size and degree of unsaturation. Phospholipids are ubiquitous
components of all biological membranes.
Protein - Large organic molecules involved in all aspects of cell structure and function,
synthesized by ribosomes from amino acid building blocks.
Reduction - In chemistry, reduction refers to the reaction of hydrogen with another substance or
the chemical reaction in which an element gains an electron.
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Scaffold - Three-dimensional biodegradable polymers engineered for cell growth.
Self-assembly - At the molecular level, the spontaneous gathering of molecules into welldefined, stable, structures that are held together by intermolecular forces. In chemical solutions,
self-assembly (also called Brownian assembly) results from the random motion of molecules and
the affinity of their binding sites for one another. Self-assembly also refers to the joining of
complementary surfaces in nanomolecular interaction. Developing simple, efficient methods to
organize molecules and molecular clusters into precise, pre-determined structures is an
important area of nanotechnology exploration.
Solvent -- A liquid that dissolves other molecular components to form a stable and
homogeneous solution. In biological systems, the solvent is water.
Solute -- A molecule or ion that can be dissolved in a solvent to form a solution. In general,
hydrophobic (nonpolar) molecules dissolve in hydrophobic (nonpolar) solvents, and hydrophilic
(polar) molecules dissolve in hydrophilic (polar) solvents.
Supramolecular structure -- Complex assemblies of multiple structures, such as multienzyme
complexes, microtubules, biological membranes, viral envelopes, cell walls, and other cellular
structures.
Vesicles - In cell biology, a relatively small and enclosed compartment, separated from the
cytosol by at least one lipid bilayer. Cellular vesicles store, transport, or digest cellular products
and wastes.
Related SCME Learning Modules





BioMEMS Overview
BioMEMS Applications Overview
DNA Overview
DNA to Protein Overview
Cells: The Building Blocks of Life
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Disclaimer
The information contained herein is considered to be true and accurate; however the Southwest Center
for Microsystems Education (SCME) makes no guarantees concerning the authenticity of any statement.
SCME accepts no liability for the content of this unit, or for the consequences of any actions taken on
the basis of the information provided.
Support for this work was provided by the National Science Foundation's Advanced
Technological Education (ATE) Program.
This Learning Module was developed in conjunction with Bio-Link, a National Science
Foundation Advanced Technological Education (ATE) Center for Biotechnology @ www.biolink.org.
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Biomolecular Applications for bioMEMS PK
Biomolecular Functions - Activity
Biomolecular Applications for bioMEMS
Participant Guide
Description and Estimated Time to Complete
This activity provides you with the opportunity to think about the functions of biomolecules by
comparing them to macroscopic equivalent components.
Estimated Time to Complete
Allow at least 30 minutes to complete
Introduction
The three types of biomolecules that can be used in bioMEMS biological interfaces include the
following:
 Nucleic acids, such as DNA. These are the molecules that cells use to carry genetic
information.
 Proteins, such as enzymes, fibers, molecular motors, channels and pores, vesicles. These
molecules are often referred to as the "work horses" of the cell because they perform so many
of the jobs of cellular metabolism.
 Lipids, such as phospholipid vesicles and membranes. These are relatively small molecules
that self-assemble into very thin membranes in order to make separate compartments in the cell.
They also provide a membrane barrier on the outside of all cells.
Activity Objectives and Outcomes
Activity Objectives
 Demonstrate your understanding of biomolecule functions by comparing their functions to
equivalent macroscopic components.
Activity Outcomes
In this activity you will make the connection between familiar functions and those of biomolecules.
The keywords and referenced glossaries in the primary knowledge unit may be useful in
completing this activity.
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Biomolecular Functions Activity
Activity: Biomolecules' Functions
In the following table, list a function(s) performed by each of the biological molecules and an
equivalent macroscopic component.
Macroscopic
components
struts, beams, casings
Function
Molecular example(s)
actin microfilament structures
cables
collagen
fasteners, glue
intermolecular forces
solenoids, actuators
boat motors
conformation-changing proteins,
actin/myosin, kinesin/microtubules
flagellar motor
drive shafts
bacterial flagella
containers
vesicles
pipes
various tubular structures
pumps
flagella, transmembrane proteins
highways
microtubules
automobiles
kinesin
Clamps
enzymatic binding sites, cell surface
receptors
ATP synthase
Electric generators
Table 1: Biomolecules and their Functions
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Biomolecular Functions Activity
Summary
Biomolecules provide functional specificity useful for biosensing, chemical conversions, and
separations in bioMEMS design. Most of these functions such as transducing and moving fluids are
the same functions as macroscopic components.
Disclaimer
The information contained herein is considered to be true and accurate; however the Southwest Center for
Microsystems Education (SCME) makes no guarantees concerning the authenticity of any statement. SCME
accepts no liability for the content of this unit, or for the consequences of any actions taken on the basis of
the information provided.
Unit Evaluation
The Southwest Center for Microsystems Education (SCME) would like your feedback on this
activity. Your feedback allows SCME to maintain the quality and relevance of this material.
To provide feedback, please visit http://www.scme-nm.org/ . Click on SCO Feedback.
Your feedback is greatly appreciated.
Activity Contributors
Developer and Subject Matter Expert
Trish Phelps, PhD
Austin Community College
Editors
Mary Jane Willis, Instructional Design
Barbara C. Lopez, Research Engineer, University of New Mexico
Support for this work was provided by the National Science Foundation's Advanced Technological
Education (ATE) Program.
This Learning Module was developed in conjunction with Bio-Link, a National Science Foundation
Advanced Technological Education (ATE) Center for Biotechnology @ www.bio-link.org.
Southwest Center for Microsystems Education (SCME)
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Biomolecular Functions Activity
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Biomolecular Functions Activity
Southwest Center for Microsystems Education (SCME)
University of New Mexico
MEMS BioMEMS Topic
The Scale of Biomolecules
Activity SCO
This SCO is part of the Learning Module
Biomolecular Applications for bioMEMS
Target audiences: High School, Community College.
Support for this work was provided by the National Science Foundation's Advanced Technological Education
(ATE) Program through Grants #DUE 0830384 and 0902411.
This Learning Module was developed in conjunction with Bio-Link, a National Science Foundation Advanced
Technological Education (ATE) Center for Biotechnology @ www.bio-link.org.
Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors
and creators, and do not necessarily reflect the views of the National Science Foundation.
Copyright 2009 - 2011 by the Southwest Center for Microsystems Education
and
The Regents of the University of New Mexico
Southwest Center for Microsystems Education (SCME)
800 Bradbury Drive SE, Suite 235
Albuquerque, NM 87106-4346
Phone: 505-272-7150
Website: www.scme-nm.org email contact: [email protected]
The Scale of Biomolecules - Activity
Activity SCO
Participant Guide
Description and Estimated Time to Complete
This activity allows you to explore the relationship between the sizes of different molecules and
cells. An understanding of the size of cells and molecules allows you to better understand how
these components can be used within MEMS devices and as bioMEMS devices.
Estimated Time to Complete
Allow approximately 45 minutes to complete
Introduction
Nanoscience is concerned with the study of novel phenomena and properties of materials that occur
at extremely small scales. Nanotechnology is the application of nanoscale science, engineering and
technology to produce novel materials and devices.
"Nanotechnology is the understanding and control of matter at dimensions of roughly 1 to 100
nanometers, where unique phenomena enable novel applications. Encompassing nanoscale science,
engineering and technology, nanotechnology involves imaging, measuring, modeling, and
manipulating matter at this length scale. " National Nanotechnology Initiative (NNI)
BioMEMS is one of the outcomes of the merging of Nanotechnology and Microelectromechanical
Systems (MEMS). Biomolecules are enabling the design and fabrication of MEMS devices with
components in both the micro and nanoscales. BioMEMS takes advantage of the properties of
biomolecules to do the same work as fabricated components.
To better understand Micro and Nanotechnologies, it is important to understand the components and
the size of these components relative to each other.
Activity Objectives and Outcomes
Activity Objectives
 Demonstrate your understanding of the relative size of biomolecules by creating an illustration
that consists of correctly proportioned molecules joined to other molecules and cells.
Activity Outcomes
You will be become familiar with the scale of cells and biomolecules. This knowledge will assist
you in the design of a bioMEMS. (See the "Biomolecular Applications – Activity")
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The Scale of Biomolecules Activity
Supplies
This activity can be completed using a graphics software program such as PowerPoint. If no such
program is available, then a paper graphic can be constructed with the following supplies.
Per participant or team
One large sheet of graph paper
Ruler
Colored markers
Pictures of items in the following table - "Relative size of Biomolecules in Nanometers". Pictures
can be drawn or downloaded from the internet. If downloaded, adjust the size of each object
relative to the size given in the activity table before printing.
Activity – The Scale of Biomolecules
Using a large sheet of graph paper or a graphic program, create a graphic of the following:
A red blood cell attached to a spore, which is attached to a bacterium, which is attached to a
liposome vesicle, attached to a tobacco mosaic virus.
Add a porin channel to the lipsome vesicle.
Place a 10,000 nm long flagellum on the bacterium.
Even though your graphic will be in the macroscale, you must maintain the correct proportion to
the actual sizes of the objects. The actual size of each object is listed in the following table.
Variation of activity: Create a scaled graphic of ALL of the objects in the table illustrating the
correct size proportions.
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The Scale of Biomolecules Activity
Table: Relative Size of Biomolecules in Nanometers
Object
Hydrogen atom
Water molecule, H2O
Amino acid
DNA (width)
Cell membrane
Ferritin iron-storage
protein
Bacterial S-layer
Porin channel
Actin filament
Intermediate filament
Microtubule
Bacterial flagellum
Tobacco mosaic virus
Magnetosome crystals
Liposome vesicle
Pores in synthetic
membrane
Bacterial cell
Spores
Red blood cell
Human hair
Diameter (nm)
0.1
0.3
1
2.5
5-9
12
5-35
4-10
5-9
10
25
12-25
18
35-150
100 (minimum)
Inside diameter (nm)
8
2-8
2-3
12-15
2-3
4
85 (minimum)
200 (minimum)
250 (minimum)
1000 (maximum)
1,000-8,000
6,000-8,000
60,000 to 100,000
Summary
It is important to understand the actual size of an object to better understand its function and
application in a bioMEMS device. The nanoscale of biomolecules enables functions to be
performed that were not possible a few years ago. We now have the technology to manipulate
nanosize objects that can further manipulate or destroy single cells.
References
 Biomolecular Applications for bioMEMS
 DNA Overview
 DNA to Protein Overview
 Cells: The Building Blocks of Life
Support for this work was provided by the National Science Foundation's Advanced
Technological Education (ATE) Program. This Learning Module was developed in
conjunction with Bio-Link, a National Science Foundation Advanced Technological Education
(ATE) Center for Biotechnology @ www.bio-link.org.
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The Scale of Biomolecules Activity
Biological Motors - Activity
Biomolecular Applications of bioMEMS
Participant Guide
Description and Estimated Time to Complete
This activity provides the opportunity for you to explore the movement and function of molecular
motors and the generation of the energy that powers them.
Estimated Time to Complete
Allow at least 45 minutes to complete this activity.
Introduction
All cellular receptors and enzymes are molecular machines because they all have moving parts.
There are molecular motors that have linear motion along cytoskeletal elements (microtubules or
actin microfilaments) within the cell. There are also rotary motors that spin on an axis within a cell.
Just as macro-motors need fuel to operate, molecular motors also need fuel. Their fuel comes in the
form of a high energy molecule called adenosine triphosphate (ATP). This molecule gives up its
chemical energy when it is hydrolyzed into adenosine diphosphate (ADP) and phosphate molecules.
The surrendered chemical energy is then transduced to the mechanical energy of the molecular
motor.
In a bioMEMS device, molecular motors can act as actuators that are controlled by the availability
of "fuel" or ATP.
Activity Objectives and Outcomes
Activity Objectives
 Demonstrate your understanding of molecule motors by watching three (3) on-line movies and
correctly answering questions at the end of each movie.
Activity Outcomes
In this activity you will become familiar with how ATP is created and used for energy, and how
molecular motors move.
Resources
Computer with high-speed Internet access.
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Biological Motors Activity
Documentation
In this activity you will review three (3) on-line animated movies:
ATP Synthase Enzyme (http://vcell.ndsu.nodak.edu/animations/atpgradient/movie.htm)
Flagellum Motor Protein (http://www.arn.org/docs/mm/flag_dithani.gif)
Kinesin Motor Protein (http://valelab.ucsf.edu/)
For your documentation, answer the questions at the end of each procedure for each animation.
Write a brief summary of the basic concepts presented in each animated movie.
Procedure 1: ATP Synthase Enzyme
1. Go to the following website: http://vcell.ndsu.nodak.edu/animations/atpgradient/movie.htm
2. Watch the animation: ATP Synthase Gradient, the Movie.
3. Write a brief summary of the basic concepts introduced.
4. Answer the following questions.
a. What propels the rotation of the ATP synthase?
b. ATP is the product of this enzyme. What are the substrates for this
reaction?
c. How many protons (hydrogen ions) must pass through the channel to
synthesize each ATP molecule?
d. What would you have to do in order to assemble an ATP synthase
molecule to power an ATP energy-requiring biomolecule on a bioMEMS
device? How would you turn ATP synthase activity on? How could you
turn ATP synthase activity off?
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Biological Motors Activity
Procedure 2: Flagellum Motor Protein
1. Go to the following website: http://www.arn.org/docs/mm/flag_dithani.gif
2. Watch the animation of the movement of a flagellum motor protein.
3. Write a brief summary of the basic concepts introduced.
4. Answer the following questions.
a. What type of motion does this motor protein make?
b. What is attached to the motor that provides the locomotion to a bacterium?
c. What fuels the motion of a flagellum motor protein?
d. What causes locomotion when a flagellum motor protein is moving?
Procedure 3: Kinesin Motor Protein
1. Go to the following website: http://valelab.ucsf.edu/ (Animated model of processive motion by
conventional kinesin) or
http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/movies/kinesin.dcr (Movement
of Kinesin Motor Protein – Shockwave file)
2. Watch the animations.
3. Write a brief summary of the basic concepts introduced.
4. Answer the following questions.
a. What is the structure called that the kinesin molecule is "walking" along?
b. What is the direct effect of ATP binding and hydrolysis on the motion of the kinesin
molecule?
c. What would stop, start, and speed up such a motor that is applied to a bioMEMS
surface?
d. What controls the direction that the kinesin moves on a bioMEMS surface?
e. What would allow a kinesin motor protein to carry cargo, such as a membrane vesicle or
nanoparticle?
Summary
The range of movement in molecular motors is generally very small and subtle, on the order of
nanometers. Some molecular motors transport "cargo". Others are responsible for providing
locomotion for the cell itself, or for transporting particles within the cell. They are all controlled by
the availability of ATP fuel.
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Biological Motors Activity
Resources – SCME Learning Modules
 Biomolecular Applications for bioMEMS
 DNA Overview
 DNA to Protein Overview
 Cells: The Building Blocks of Life
Support for this work was provided by the National Science Foundation's Advanced Technological
Education (ATE) Program.
This Learning Module was developed in conjunction with Bio-Link, a National Science Foundation
Advanced Technological Education (ATE) Center for Biotechnology @ www.bio-link.org.
Southwest Center for Microsystems Education (SCME)
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Biological Motors Activity
Southwest Center for Microsystems Education (SCME)
Learning Modules available for download @ scme-nm.org
MEMS Introductory Topics
MEMS Fabrication
MEMS History
MEMS: Making Micro Machines DVD and LM
Units of Weights and Measures
A Comparison of Scale: Macro, Micro, and Nano
Introduction to Transducers, Sensors and Actuators
Wheatstone Bridge (Activity Kit available)
MEMS Applications Overview
Microcantilevers (Activity Kit available)
Micropumps
MEMS Micromachining Overview
Manufacturing Technology Training Center Pressure
Sensor Process (Activity Kits available)
Crystallography for Microsystems (Activity Kits
available)
Photolithography Overview for Microsystems
Etch Overview for Microsystems (Activity Kits
available)
Deposition Overview Microsystems
Oxidation Overview for Microsystems (Activity Kit
available)
MEMS Innovators Activity (Activity Kit available)
BioMEMS
Safety
BioMEMS Overview
BioMEMS Applications Overview
DNA Overview
DNA to Protein Overview
Cells – The Building Blocks of Life
Biomolecular Applications for bioMEMS
BioMEMS Therapeutics Overview
BioMEMS Diagnostics Overview
Clinical Laboratory Techniques and MEMS
MEMS for Environmental and Bioterrorism
Applications
Regulations of bioMEMS
Hazardous Materials
Chemical Lab Safety
Material Safety Data Sheets
Interpreting Chemical Labels / NFPA
Personal Protective Equipment (PPE)
MEMS Applications
Revision: 2/17/2010
Check the our website regularly for updates
and new Learning Modules.
For more information about SCME
and its Learning Modules and kits,
visit our website
scme-nm.org or contact
Dr. Matthias Pleil at
[email protected]
www.scme-nm.org