Processive bio-molecular motors, which move actively along cytoskeletal
filaments, drive the cargo traffic in cells and in biomimetic systems.
A single motor molecule is sufficient for continuous transport of
cargoes such as vesicles or latex beads over a few micrometers. To
achieve transport over larger distances, several motor molecules have
to cooperate. Scientists from the Max Planck Institute of Colloids and
Interfaces in Potsdam have now developed a new theory that only seven
or eight motor molecules are sufficient for directed transport over
centimeters or even meters. They also show that an applied load force,
which is shared by the pulling motors, strongly reduces the cargo
velocity and leads to a highly nonlinear force-velocity relationship
(PNAS, Advanced Online Publication, November 14-18, 2005).
Molecular motors are nano-tractors for all kinds of cargo within the
cells of living beings. They move in a stepwise manner along filaments
of the cytoskeleton, consuming energy provided by the hydrolysis of
ATP, which can be considered the fuel of the cell. Kinesin and dynein
motors move along microtubules and myosins move along actin filaments.
The step sizes of these motors are of the order of 10 nm. By stepping
in a directed fash-ion along filaments, the motors pull cargo particles
which are much larger than the mo-tors themselves. In addition to their
importance for the functioning of cells, molecular motors have many
possible applications as biomimetic transport systems and are likely to
become a key component in the emerging bio-nanotechnology.
Active transport driven by molecular motors is particularly
important for nerve cells, or neurons. These cells have extended
compartments, axons, which connect the cell body with the synapse,
where the nerve signals are transmitted from one neuron to another. The
length of axons is in the centimeter or even meter range; examples of
relatively long axons are those that connect our spinal cord with the
tips of our fingers and toes. Within such an axon, microtubules provide
the tracks along which molecular motors transport their cargo, such as
vesicles filled with neurotransmitters.
During the last decade, our knowledge about molecular motors has
increased rapidly. This was mainly due to the development of powerful
single molecule experiments and biomimetic model systems which permit
the study of molecular motors outside cells in a systematic fashion.
One example is the bead assay, where filaments are immobilized on a
surface. Molecular motors pull latex beads along these filaments, and
the movement of the beads is observed under the microscope.
One important result of these experiments is that molecular motors,
unlike railways or cars, have a strong tendency to fall off their track
and diffuse away into the surrounding aqueous solution. This is a
direct consequence of their nanoscale size which makes them rather
susceptible to thermal noise. Thus, a single molecular motor can only
’grab’ onto the filament for a relatively short time, on the order of
one second. During this time, a single motor covers about one
micrometer, which represents only a tiny fraction, about 1/10000, of
the long transport distances for cargo particles in axons. In other
words, a single motor behaves much like a sprinter, whereas the whole
cargo performs a mara-thon.
Scientists of the Max Planck Institute of Colloids and Interfaces in
Potsdam have now provided a simple solution to this puzzle. If the
cargo is pulled by several motors as shown in Fig.1, any motor that
unbinds from the filament will stay close to that filament as long as
the cargo and filament are still cross-linked by at least one bound
motor. In such a situation, the unbound motor can rebind to the
filament and then continue to pull the cargo – in contrast to human
sprinters, molecular motors don’t get tired.
This mechanism has been derived from a new theoretical model, which
distinguishes the different bound states of the cargo particle and
describes the transitions between these states. Using this model, the
Max Planck scientists have been able to calculate several transport
properties, such as the average velocity and the average walking
distance of the cargo particle as a function of the maximum number of
motors that can pull this par-ticle. For kinesin motors, for example,
calculations show that only seven or eight motors are sufficient for
the transport over centimeter distances and that a cargo particle
pulled by 10 motors has an average walking distance of about 1 meter.
If molecular motors move against an external load force, this force
is shared among the pulling motors. One obvious consequence is that the
movement of the cargo is slowed down. In addition, the force felt by
each pulling motor strongly increases the unbinding probability for
such a motor. Furthermore, as more motors unbind, each of the remaining
pulling motors has to sustain a larger force, which would mean that
their unbinding probability increases even further. This leads to a
cascade of unbinding processes and to a strongly nonlinear dependence
of the cargo velocity on the external load force. Simi-lar cascade
processes are expected in more complex situations, in which the cargo
transport is performed by different types of molecular motors.
All transport properties predicted by the new theory can be
investigated in experiments using techniques which have been developed
for single motors. In fact, preliminary ex-periments at the Max Planck
Institute in Potsdam agree with the theoretical predictions. Likewise,
the quantitative theory should also be useful in order to design
biomimetic transport systems for lab-on-a-chip applications — in
which, for example, molecular mo-tors transport certain molecules to
specific reaction sites. Depending on the arrange-ment of the filaments
in these systems, varying the travel distance provides a strategy to
control either the localization of the reagents to their target sites
or, alternatively, their diffusion, which is enhanced by motor-driven
Source: Max Planck Society. November 2005.