Molecular Motors
Neil Thomas,
University of Birmingham,
UK.
ニール トーマス
バーミンガム大学
イギリス
Acknowledgements
My thanks to:
• The British Council (Tsuji-san & Shimura-san)
• Monbukagakusho, JSPS & JST
• Dr Yasuhiro Imafuku (Kyushu University)
• Dr Shinji Kamimura (Tokyo University)
2
Birmingham University
The University was established in 1905.
It now has over 15000 students.
3
Birmingham and the UK
Birmingham is England’s second city.
It is in the Midlands, about 200 km north-west of London.
4
Canals and Railways
Birmingham is at the
centre
of England's canal system.
Canals were once very
important for carrying
materials for industry.
Nowadays, 'narrow boats'
can be hired for leisure.
Railways were built from
about 1830.
The trains were pulled by
steam locomotives.
Photo: Brian Townsley
The 'Age of Steam' made
Britain very wealthy.
5
James Watt
James Watt (1736-1819), pioneer of
the steam engine, worked with
Matthew Boulton in Birmingham.
He invented the condenser and the
governor.
Watt’s Beam Engine
Animation: Matt Keveney
Steam engines led to the science of Thermodynamics.
6
Molecular Motors & Movement
I’m a physics lecturer.
My main research interest is the
molecular motors that produce
movement in living systems, from
single cells to whole animals.
A single-celled amoeba
This seminar will show you
why molecular motors are
an exciting and important
topic.
A galloping horse
7
Outline of Seminar
How Muscles Work
How Cells Make DNA
How Cells Move
How Cells Generate Energy
8
Videos from Essential Cell Biology CD-ROM
Muscles & Movement
Cheetah
Humming-bird
Shark
Bumble-bee
Videos from How Animals Move CD-ROM
9
Muscles
Human arm muscles
Structure of muscle
Diagrams from The Ultimate Human Body CD-ROM
10
Bundle of Muscle Fibres
(viewed with an optical microscope)
• Fibres show a periodic striation pattern
• Black ‘blobs’ are cell nuclei
11
Photo from How Animals Move CD-ROM
Single fibre of striated muscle
• Muscle fibres are single biological cells
• Fibre diameter is typically about 100 microns (0.1 mm)
• Fibres consist of bundles of smaller myofibrils
12
Photo from How Animals Move CD-ROM
Single myofibril
(viewed with an electron microscope)
• Each myofibril is about 1 micron in diameter
• Myofibrils also show the periodic striation pattern
• The repeating unit is called a sarcomere
13
Photo from How Animals Move CD-ROM
Muscle Contraction
(Sliding-filament model)
A nervous impulse (guided by T-tubules) causes the
release of calcium inside a muscle cell.
Calcium switches on the molecular motors that cause
sliding of the actin and myosin filaments.
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Video from Essential Cell Biology CD-ROM
Actomyosin: the molecular motor
that powers our muscles
Video from Essential Cell
Biology CD-ROM
• The actomyosin motor works in a cycle.
• Myosin binds to actin, its lever arm tilts over, and then
it detaches.
• Each cycle uses up one molecule of ATP.
• ATP is the ‘fuel’ that allows the motor to perform
work.
• The chemical reaction is ATP → ADP + Pi
15
Heat Engines Work in a
Thermodynamic Cycle
Steam Engine (Rankine
Cycle)
Animations: Matt Keveney
Car Engine (Otto Cycle)
Actomyosin also works in a cycle.
Its power stroke is only 5 – 10 nm.
(1 million nanometres = 1 millimetre)
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We apply Thermodynamics to molecular motors.
Cilia and Flagella
Cilia (Stentor)
Beating cilia
(Simulation)
Flagellum (Sperm)
Beating flagellum
(Simulation)
Videos from How Animals Move CD-ROM
17
Molecular Motors in Cilia
Dynein motors cause
sliding of microtubules.
Sliding produces bending:
Cross-section of a cilium
showing microtubules
and dynein arms.
(Diameter = 250 nm)
Cilia and flagella beat spontaneously!
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How Do Cells Move?
A keratocyte (from a fish
scale) crawls rapidly .
An amoeba moves rapidly
by extending pseudopodia.
Neurites grow slowly from
nerve cells by means of
growth cones.
19
Cells move by using their
cytoskeleton.
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The Cytoskeleton
Actin filaments (red) allow the cell to crawl.
Microtubules (blue) transport chemical signals that
control the movement.
Intermediate filaments (green) add strength to the cell.
21
Photo from Video Tour of Cell Motility by Vic Small
Crawling Cancer Cell
Formation of actin filaments inside the lamellipodium
pushes the front of the cell forwards.
The rear of the cell is pulled along by actomyosin.
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From Video Tour of Cell Motility by Vic Small
Crawling of white blood cells
A neutrophil chases a
bacterium.
Lymphocytes migrate to a
wound.
In both cases, the movement is in response to a
chemical signal (‘chemotaxis’).
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From Video Tour of Cell Motility by Vic Small
Propulsion by Actin
An actin filament moves by
‘treadmilling’.
The motion consumes ATP.
From Video Tour of Cell Motility by Vic Small
Listeria bacteria
move by ‘hijacking’
a cell’s actin.
Video from Essential Cell Biology CD-ROM
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Movement inside Cells
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Organelle Movement
Molecular motors transport material along the cytoskeleton.
The video shows organelle transport along a microtubule.
Kinesin motors transport material to the ‘plus’ end (away
from the nucleus).
Dynein motors transport material in the opposite direction.
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Video from Essential Cell Biology CD-ROM
The Kinesin Molecular Motor
Video from Essential Cell
Biology CD-ROM
The video shows how two-headed kinesin may step
along a microtubule.
The model is based on many different experiments.
We have used a similar picture to develop a
mathematical model of the kinesin motor for
analysing the results of laser-tweezer experiments.
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Laser Tweezers
Laser tweezers are used to trap tiny beads in a focussed
laser beam.
They exert a force comparable to that due to a single
molecular motor (typically a few piconewtons).
1 gram weighs about 10 thousand million piconewtons
Video from Essential Cell Biology CD-ROM
28
Laser Tweezers
Visscher et al. (1999)
Laser tweezers are used to study kinesin stepping along
a microtubule.
The kinesin molecule is attached to a bead that is
trapped in the focussed laser beam.
The tweezers exert a force that slows down the kinesin 29
motor.
Molecular Motors and DNA
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DNA carries the Genetic Code
• A DNA molecule is a double helix (like a spiral staircase)
• The two strands of the helix are joined by base pairs
• Base C always pairs with base G
• Base A always pairs with base T
• The sequence of bases CAA… stores the genetic information
31
Videos from Essential Cell Biology CD-ROM
DNA Motors 1:Transcription
(Reading a single gene)
The RNA polymerase motor copies (transcribes) a
gene from DNA to RNA inside the cell nucleus.
Video from Essential Cell Biology CD-ROM
32
DNA Motors 2: Translation
(Making a protein from a gene)
A ribosome translates the genetic code in the
RNA to make a protein from the correct sequence
of amino acids.
Our bone marrow makes 100 million million
molecules of haemoglobin per second.
Video from Essential Cell Biology CD-ROM
33
DNA motors 3: Replication
(Making an exact copy of DNA)
A DNA helicase
motor separates the
DNA double helix
into two strands.
DNA polymerase
motors copy each
strand.
Videos from Essential Cell Biology CD-ROM
34
DNA Motors 4: Mitosis
(Cell division)
Microtubules form a
spindle (green).
Pairs of chromosomes
containing DNA (blue)
attach to the spindle by
kinetochores (pink) along
the equator.
Cells in a frog embryo
divide rapidly.
Molecular motors pull
chromosomes to opposite
poles of the spindle.
Each cell gets the same
DNA.
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Videos from Essential Cell Biology CD-ROM
How Do Cells Generate Energy?
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Mitochondria: the Cell’s Power-Stations
A heart muscle cell contains
myofibrils (orange). It requires
many mitochondria (red),
which supply ATP for the
actomyosin molecular motors.
Glucose oxidation
produces protons in the
inter-membrane space.
Proton flow back across
the inner membrane
generates ATP.
37
ATP Synthase: A Molecular
Turbine
ATP synthase is a molecular
turbine that converts energy
from a proton gradient into
the chemical energy in the
form of ATP that powers the
cell.
The molecular structure
illustrates how ATP may
be synthesized.
38
Rotation of ATP Synthase
Kinoshita et al. 1998
Kinoshita and colleagues
observed rotation of ATP
synthase by attaching a
fluorescent actin filament
to the shaft.
39
Electricity Generation
A steam turbine rotates a
generator to produce electricity.
The Chiba #1 turbine generator
produced 125 MW (125 million
watts).
#1 Turbine from Chiba
Thermal Power Station
(TEPCO Museum)
A marine turbine from a ship
40
Turbines Compared
Chiba #1 Turbine
TEPCO Museum (Kawasaki).
The Chiba steam turbine is over
10 m long.
It can generate about 100
million watts (108 W = 100 MW).
ATP synthase is about 20 nm long.
It generates 1/(million million million)
watts (10-18 W =1 aW).
Both machines are governed
by the laws of
Thermodynamics.
41
Summary
• Molecular motors are the fundamental
agents of movement in living systems
• They are cyclic machines like steam
engines
• They generally consume one molecule of
ATP per cycle
• They typically produce force ∼1 pN and
power ~ 1 aW
42
But molecular motors working
together in muscle can produce
large forces…
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終
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