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Motor Transport in Bio-Nano Systems
Max Planck researchers determine
optimal parameters for biomimetic transport systems
based on molecular motors
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Molecular
motors are nanoscale engines which move along very
thin rod-like filaments and, in this way, drive the
heavy traffic of molecular cargo within biological
cells. Both motors and filaments can be isolated
from the cells and used to construct biomimetic transport
systems. In order to increase the flux of the cargo
transport, it would be necessary to increase the
number of motors that contribute to this transport
but, at the same time, avoid the build-up of traffic
jams. Scientists from the Max Planck Institute of
Colloids and Interfaces in Potsdam and from the University
of Amsterdam have now modelled and simulated the
motor traffic for different compartment geometries
and filament arrangements, and have determined the
optimal conditions for the transport of nanocargo
in these systems (Biophysical Journal, 88, 3118-3132,
May 2005).
Each cell of our body contains a huge number of small
vesicles which exhibit complex patterns of intracellular
traffic: some vesicles travel from the cell center to
the periphery and vice versa, some shuttle between different
organelles or cellular compartments. An extreme case
is provided by the long-ranged transport of vesicles
and organelles along the axons between our nerve cells,
which can be as long as half a meter. All of these movements
are based on two molecular components: very thin rod-like
filaments, which form a complex network of rails, and
molecular motors, which move along those filaments and
carry vesicles and other nanocargo along. When bound
to the filaments, the motors are able to transform the
chemical energy of a single ATP molecule into mechanical
work. In this way, they can utilize the smallest possible
amount of fuel.
Both filaments and motors can be isolated from biological
cells and used to construct biomimetic transport systems.
A relatively simple example for such a system consists
of filaments which are aligned on a substrate surface as shown in Figure 1. The
filaments are polar and have two different ends, a ‘plus' end and a ‘minus' end.
In Figure 1, the filaments are arranged in such a way that all ‘plus' ends point
into the same direction. Such an arrangement provides many parallel tracks for
the molecular motors and, thus, represents a multi-lane highway in the nanoregime.
Using such a biomimetic model system, scientists can study the transport properties
in a quantitative manner, identify useful control parameters, and determine the
functional dependence of the transport properties on these parameters. This is
the only possible strategy to obtain the basic knowledge that is necessary to
improve the system design and to optimize its performance.
We now have a basic understanding of the behavior of single motors. These motors
are dimeric proteins with two legs, which make discrete steps along the filament.
Each step corresponds to a motor displacement of about 10 nanometers, comparable
to the size of its legs. In one second, the motor makes about 100 steps which
leads to a velocity of about one micrometer per second. The absolute value of
this velocity is not very impressive, but relative to its size, the motor molecule
moves very fast: indeed, on the macroscopic scale, its movement would correspond
to an athlete who runs 200 meters in one second! This is even more surprising
if one realizes that the motor moves in a very viscous environment since it steadily
undergoes many collisions with a large number of water molecules. Because of
these collisions, the molecular motor has a finite run length: After a few seconds,
it unbinds from its track and performs random Brownian motion in the surrounding
water until it rebinds to the same or another filament.
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Fig.
1: Three snapshots showing the transport of a micrometer
bead (white arrow) at 0, 4, and 8 seconds. The
bead is pulled by molecular motors, which are too
small to be visible, along parallel filaments,
which are immobilized on a substrate surface. All
filaments are aligned in such a way that their ‘plus'
ends point to the right and form a multi-lane highway
in the nanoregime. The bead moves about 8 micrometers
in 8 seconds; during this time, each motor makes
about 800 steps.
Image: Max Planck Institute of Colloids and Interfaces
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In
order to understand the motor traffic in biological
cells and in biomimetic systems, it is necessary to
go beyond the single motor level and consider the cooperative
behavior of many motors. To obtain a large flux of
cargo transport, it is obviously useful to let many
motors work in parallel. However, when several motors
move along the same track, they start to bump into
each other and to form molecular traffic jams. These
jams are similar to the jams on our highways but there
are also important differences. First, the molecular
motors cannot `see' other motors and their cargo before
they bump into them. Second, in contrast to our cars,
which cannot leave the highway when they are caught
in a jam, the molecular motors can unbind from the
filament and, thus, escape into the third dimension.
In order to study these complex patterns of movements, the Max Planck researchers
have developed new theoretical models which are based on the known properties
of single motors and which enable them to study the cooperative behavior of many
motors and their interactions. In the framework of these models, one can determine
the functional dependence of the motor transport on the compartment geometry
and on the arrangement of the filaments. Two particularly interesting architectures
are uniaxial arrangements of filaments within tube-like compartments, which resemble
axons of nerve cells, see Figure 2, and radial arrangements of filaments within
disk-like compartments, which resemble large cells adhering to a substrate surface. |
Fig.
2: (Top) Schematic diagram of molecular motors
that run along a single filament or diffuse in
the surrounding water. The running motors form
a traffic jam close to the ‘plus' end of the filament.
(Bottom) The jamming effect depends strongly on
the compartment geometry and is much more pronounced
in uniaxial systems (left) than in radial systems
(right).
Image: Max Planck Institute of Colloids and Interfaces
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Surprisingly,
the geometry of the system has a rather strong effect
on the build-up of traffic jams. In uniaxial systems,
traffic jams cannot be avoided as one increases the
number of motors involved in the cargo transport. In
radial systems, on the other hand, jams can be avoided,
to a large extent, provided the motors leave the filament
sufficiently fast after they have reached its ‘plus'
end. However, both types of systems exhibit a characteristic,
intermediate motor concentration for which the cargo
transport is optimal. With the models the researchers
can predict how this optimal motor concentration depends
on the single motor properties.
The theoretical results are in agreement with the available experimental data,
both for biomimetic systems and for biological cells. The theory has been extended
to more complex systems such as two-way traffic of two motor species that move
along the same filament but in opposite directions. The latter system exhibits
a genuine phase transition from a low flux to a high flux state. Likewise, regular
patterns of filaments have been shown to lead to enhanced motor diffusion along
the substrate surface. All of these results have been obtained from a combination
of analytical calculations and computer simulations.
These theories can guide the design of new transport systems by exploring different
system architectures in a systematic way before they are actually constructed
in the lab. The enhanced diffusion of motors at regular patterns of filaments
provides an instructive example: When integrated into existing microarrays for
DNA and RNA hybridization, these transport systems would act to increase the
hybridization rates.
In general, biomimetic systems based on molecular motors and filaments have many
potential applications in bionanotechnology, pharmacology, and medicine. During
the next couple of years, we may witness the development of sorting devices for
biomolecules and biocolloids, drug delivery systems that utilize the motor transport
within human cells, and motile components for nanoscale manufacturing. Long term,
we should also be able to construct `smart' biomimetic systems which are able
to respond to and `survive' in a changing environment.
Original work:
Stefan Klumpp, Theo M. Nieuwenhuizen, and Reinhard Lipowsky
Self-organized density patterns of molecular motors in arrays of cytoskeletal
filaments
Biophysical Journal 88, 3118-3132 (2005)
Stefan Klumpp and Reinhard Lipowsky
Phase transitions in systems with two species of molecular motors
PDF (89 KB)
Contact:
Prof. Dr. Reinhard Lipowsky
Max
Planck Institute of Colloids and Interfaces , Potsdam
Tel.: +49 331 567-9600
Fax: +49 331 567-9602
E-mail: Reinhard.Lipowsky@mpikg.mpg.de
Dr. Stefan Klumpp
Max
Planck Institute of Colloids and Interfaces , Potsdam
Tel.: +49 331 567-9609
Fax: +49 331 567-9602
E-mail: Stefan.Klumpp@mpikg.mpg.de
Katja Schulze (Press and Public Relations)
Max
Planck Institute of Colloids and Interfaces , Potsdam
Tel.: +49 331-567-9203
Fax: +49 331-567-9202
E-mail: katja.schulze@mpikg.mpg.de
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This
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