2 research outputs found
Multiscale Modeling of the Nanomechanics of Microtubule Protofilaments
Large-size biomolecular systems that spontaneously assemble,
disassemble,
and self-repair by controlled inputs play fundamental roles in biology.
Microtubules (MTs), which play important roles in cell adhesion and
cell division, are a prime example. MTs serve as ″tracks″
for molecular motors, and their biomechanical functions depend on
dynamic instabilityî—¸a stochastic switching between periods
of rapid growing and shrinking. This process is controlled by many
cellular factors so that growth and shrinkage periods are correlated
with the life cycle of a cell. Resolving the molecular basis for the
action of these factors is of paramount importance for understanding
the diverse functions of MTs. We employed a multiscale modeling approach
to study the force-induced MT depolymerization by analyzing the mechanical
response of a MT protofilament to external forces. We carried out
self-organized polymer (SOP) model based simulations accelerated on
Graphics Processing Units (GPUs). This approach enabled us to follow
the mechanical behavior of the molecule on experimental time scales
using experimental force loads. We resolved the structural details
and determined the physical parameters that characterize the stretching
and bending modes of motion of a MT protofilament. The central result
is that the severing action of proteins, such as katanin and kinesin,
can be understood in terms of their mechanical coupling to a protofilament.
For example, the extraction of tubulin dimers from MT caps by katanin
can be achieved by pushing the protofilament toward the axis of the
MT cylinder, while the removal of large protofilaments curved into
″ram’s horn″ structures by kinesin is the result
of the outward bending of the protofilament. We showed that, at the
molecular level, these types of deformations are due to the anisotropic,
but homogeneous, micromechanical properties of MT protofilaments