Biomedical Engineering Reference
In-Depth Information
Self-assembled filamentous protein aggregates play an important role in the me-
chanics and self-organization of the cytoskeleton. In addition, a number of other pro-
teins interact with them and modulate their structure and dynamics. Cross-linking
proteins bind to two or more filaments together to form a dynamical gel. Molecular
motor proteins bind to filaments and hydrolyze nucleotide Adenosine triphosphate
(ATP). This process, coupled to a corresponding conformational change of the pro-
tein, turns stored chemical energy into mechanical work. Capping proteins modulate
the polymerization and depolymerization of the filaments at their ends.
A key question is how the elements of the cytoskeleton cooperate to achieve its
function. To what extent is there a “cellular” brain and how closely does it control
cellular mechanisms? How much of a role does spontaneous self-organization driven
by general physical principles play?
Much of the recent progress in the understanding of the complex structures
and processes that control the behavior and function of the cytoskeleton has been
linked to the development of new biophysical probes allowing an unprecedented view
of subcellular processes at work. Mechanical probes such as optical and magnetic
tweezers [3], atomic force microscopes [4] and micropipettes probe the response of the
elements of the cytoskeleton to locally applied forces. Visualization techniques using
fluorescence microscopy (e.g., fluorescence imaging with one-nanometer accuracy [5]
or single-molecule high-resolution colocalization [6] based on organic dyes) allow
one to follow the dynamics of single molecules inside living cells (
in vivo
), giving
insights into the microscopic processes underlying cellular dynamics. Many of these
experimental developments are reviewed in this topic.
Because of the large number of unknown components, it is also of interest
to study simplified systems consisting of a smaller number of well-characterized
elements
in vitro
. This has led to a number of experimental biophysical stud-
ies of purified solutions of cytoskeletal filaments and associated molecular motors
that have established that motor-induced activity drives the formation of a va-
riety of spatially inhomogeneous patterns, such as bundles, asters, and vortices
[7, 8, 9, 10, 11, 12, 13, 14]. These are reminiscent of some of the supramolecular
structures present in the cytoskeleton [15, 16]. The mechanical properties of fila-
ment-motor systems have also been studied, showing qualitative differences from
passive filament suspension. Because of the controlled nature of their preparation,
and the detailed knowledge of their constituents,
in vitro
studies are particularly
amenable to a quantitative description using techniques from theoretical physics.
In this review, we will be mostly concerned with describing the behavior of such
simplified systems on large time scales (times
≥
microsecond) where the atomistic
details are not important and a coarse-grained phenomenological description may
suce.
The reductionist viewpoint typified by this approach also has its drawbacks. A
simplified system necessarily can provide only a subset of the phenomena observed
in living cells because only a small fraction of the components are present. A choice
must also be made of
which
simplified system to study because different combinations
of components may give different or similar behavior. This choice must, of course, be
heavily influenced by previous experiments [7, 8]. A living cell is a highly optimized,
complex
system
of interacting agents with the ability to modulate its response to
complex changes in its environment. This complexity will be missing from simple
mechanical models described here. There is some hope, however, that this complexity
can eventually be combined with the physical picture emerging from the approach
