MAT 272/BMSE 272
Mechanical Force and Biomolecules:
Lecture 1
Introduction:
Why is force important for biomolecules?
1951: Pauling predicts alpha helix
1954: Watson and Crick propose double-helix
Late 50s: Perutz, Kendrew attain first protein
structures from X-ray crystallography
60s: Genetic code determined
70s: Amino acid sequences shown to uniquely
determine protein function (Anfinsen)
80s: Biotechnology explodes
(Molecular cloning , PCR)
90s: Genomes sequenced
A eucaryotic cell
Information must be stored in an ‘aperiodic crystal’
-Schrodinger, 1944
replication
Eucaryotic genome packaging
Folded structures
Proteins: Polypeptide
chains that fold into
globular structures with
a wide variety of
activities
Myoglobin : one chain of
153 monomers; 17 kDa
Proteasome: 28 chains of ~200 monomers each; 6.8 MDa total
A single-stranded RNA molecule can fold
into an enzymatically active structure (a
ribozyme)
1
3
4
2
How can you measure single molecules?
1) With electrical current
through an ion channel
(Neher and Sackmann, Nobel
Prize 1991)
2) With a fluorescent dye
3) With manipulation
That is, applying a relevant
force to a biomolecule, and
measuring resulting changes
in length
From Nobel prize announcement
Single kinesins moving along
microtubules (Vale lab website)
The common techniques
The Atomic Force
Microscope
The Optical
Tweezer
The Magnetic
Tweezer
The actuator
A cantilever
A dielectric bead A paramagnetic bead
Position
detection
Quad photodiode
Quad
photodiode
Video tracking
Force range
10-1000 pN
1-200 pN
0.1-100 pN
Advantages
Bandwidth,
sensitivity
Bandwidth,
manipulation
Simplicity, constant
force, rotation
Disadvantages
Limited low-force
ability
Complicated
Low precision in
position detection
Units, and the interesting range of force
Force~ Energy/Length; kBT ~ 4 pN nm
Length
Force
Stretching DNA
~kBT
50 nm
0.1 pN
Weak bonds
~kBT
~nm
4 pN
Unzipping DNA
2/3 H bonds
= a few kBT
~nm
10-15 pN
Motor motion
ATP ~ 20 kBT 1-10 nm 8-80 pN
[many weak
bonds]
nm
10-200
pN
Covalent bonds
1 eV ~ 40 kBT
0.1 nm
1 nN
AFM
Denaturing a
protein
Optical tweezers
Energy
Magnetic tweezers
Process
Caveat:
Reductionism
Certain proteins can
only fold in the
crowded interior of
the cell; remove the
crowding, and
you’ve removed the
physical impetus
from the problem.
Interior of an E. coli cell; from Goodsell, 1991, by
way of Alberts
green: ribosomes; red: proteins; blue: Rna
Anti-reductionism tracts
1) P. W. Anderson, Science (1972) “More is
Different”
This is the start of an argument that
eventually killed the SSC.
2) C. R. Woese, Microbio. Mol. Bio. Rev.
(2004) “A New Biology for a New Century”
In which the author questions the
significance of nearly the entire field of
molecular biology.
“If you read trendy intellectual magazines,
you may have noticed that ‘reductionism’ is one
of those things, like sin, that is only mentioned
by people who are against it. To call oneself a
reductionist will sound, in some circles, a bit like
admitting to eating babies. But, just as nobody
actually eats babies, so nobody is really a
reductionist in any sense worth being against.”
– Richard Dawkins
Practical matters
Evaluation
-Two graded problem sets (30% of grade)
-Half-lecture presentations (70%):
These will be based on a recent paper from the field. You
will get a list of papers to choose from. With my
approval, you can use a paper not on the list.
The rough plan: I give 16 lectures, students give last 2-3,
plus during final exam week (if necc.)
Prereq: Prior knowledge of stat. mech., not of bio
Note 5/28 is a UCSB holiday.
The website
http://www.engr.ucsb.edu/~saleh/#Teaching
I have posted, and will continually update:
1. PPT slides from lectures (when used)
2. pdf of lecture notes
3. pdf of journal articles referenced (e.g. Woese and
Anderson articles)
Also, there are some links to online resources (e.g.
textbooks, journal search engines) that could be
useful for background research for your presentation
Practical Matters:
The syllabus
Schedule and textbooks