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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 marathon.
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 active transport. |
