Mallik Lab. Tata
Institute of Fundamental Research,
They are small, and there are
billions of them inside you. Tiny machines, a thousandth of the thickness of
human hair, but robust and designed for an amazing variety of functions. Science fiction? Think again this is real, as real as flesh
and blood !! If you can get your hands on a high
school biology text book, flip through to the mandatory schematic of an animal
cell. Look closely, what you will see is not a floppy bag with random things
thrown in here and there. There is amazing structural organization within the
cell, with several compartments (e.g. the nucleus, Golgi
bodies, mitochondria) at specific locations. Many of
these compartments are specialized factories, each with its own assembly line
requiring specific raw material as input and generating specific products. A
constant give-and-take of materials occurs between these factories inside the
cell, because each factory is dependent on the other to function. In the big
picture of things this incessant exchange of material keeps the factories of the
cell functioning, which in turn is what keeps us alive.

This flow of material
occurs in a highly regulated and disciplined manner, so that the right things
are present at the right place and time. How does this transport of materials
take place? This is where the army of tiny machines called molecular motors
comes in. The cell has a network of roadways (one kind of roadways are called
microtubules, see Figure) with heavy traffic of molecular motors on them. These
motors can be thought of as porters ferrying all kinds of material within the
cell. You will be surprised at how well this analogy of molecular motors with
porters works, but dont forget that these motors are a 10-million times scaled
down version of what your idea of a porter is.
So, what exactly is this motor that works on a molecular scale?
One example is a protein with two legs walking along on the cellular roadway,
stepping just like a porter and carrying some cellular material as cargo.
During every step that the motor takes, it has to generate force and therefore
does some work. The energy required for this comes from chewing up a molecule
called ATP, which has energy stored in its chemical bonds. For every step that
the molecular porter takes, it needs one little packet of energy in the form of
an ATP molecule. So, if you travel inside the cell and need somebody to carry
your bags, make sure you give them a constant supply of ATP. Just three meals a
day does not work at the molecular scale.
Kinesin,
one of the best studied molecular motors walks with precise steps of 8
nanometers. For each step, kinesin uses one molecule of ATP and generates 6 piconewtons of force. A simple calculation shows that this
makes kinesin a nano-machine with almost 50%
efficiency, which is comparable to many machines of human design. To give you
an idea of the magnitude of scales here, if a kinesin motor walked upwards
starting at your toenail, it would take about 100 million steps to reach your
nose. Approximately 1 million-million kinesins would
have to team up together to arm-wrestle with you and have any hope of winning.
We are really talking nanotech here.
For anyone impressed
with kinesin, there is more to come. Dynein is a second class of motors
ferrying cargo within the cell, and is much more complicated than kinesin.
There is recent evidence that nature has implemented a nanoscale
gear mechanism within this complexity. It appears that dynein normally walks
with a step size about thrice the size of kinesin. However, if you pull dynein
backward the motor can shorten its stepsize and
resultantly produce more force, which is just like shifting gears in your car
on an uphill road. Only future research can tell why nature felt the need to
implement such complex architecture at these minute size scales.
There are many other classes of motors which I have not
discussed here for reasons of space, and also to keep the discussion simple.
One common theme that has emerged from years of research is that of
surprisingly intricate and robust architecture within these molecular motors at
a size scale which we are only now beginning to comprehend. It is these little
things in life that matter, so let us congratulate nature on a little job very
well done !!
REGULATION
OF MOLECULAR MOTORS:-
Molecular
motors with inclination to move in opposite direction (e.g. Kinesin and Dynein)
are simultaneously present on a cargo inside the cell. Infact,
multiple motors of each class are often present simultaneously on a cargo. Do
the motors work against each other (tug-of-war model), or is their relative
activity regulated by the cell (coordination model)? There is evidence that the
cell can indeed regulate the activity of different motors, such that different
kinds of cargo get localized precisely to specific locations in the cell.

FURTHER
(Follow links to download the
Papers from Pubmed website)
1.
Vale RD: The molecular motor toolbox for intracellular transport. Cell 2003, 112:467-480.
2.
Vale RD, Milligan RA: The way things move: looking under the hood of molecular
motor proteins. Science 2000, 288:88-95.
3.
Schliwa M, Woehlke G: Molecular motors.
Nature 2003, 422:759-765.
4.
Hirokawa N, Takemura R: Biochemical and molecular characterization of diseases
linked to motor proteins. Trends in Biochemical Sciences 2003, 28: 558
5.
Visscher K, Schnitzer MJ, Block SM: Single kinesin molecules studied with a molecular force
clamp.
Nature 1999, 400:184-189.
6.
Mallik R,
Carter BC, Lex SA, King SJ, Gross
SP: Cytoplasmic dynein functions as a gear in response to load.
Nature 2004, 427:649-652.
7.
Mallik R,
Gross SP: Molecular motors: strategies to get along. Curr Biol 2004, 14:R971-982.
8.
M. Welte. Bidirectional transport along microtubules
Current Biology, Vol 14, R525-37 (2004)
9.
S.P. Gross. Hither and yon: a review of bi-directional
microtubule-based transport Physical Biology, Vol 1, R1-11 (2004)
10.
A.R.
Reilein et al. Regulation of molecular motor proteins
Int Rev Cytol. Vol 204:179-238 (2001)