Modeling cell crawling
MEP or BEP - BN / Idema group - theoretical biophysics
Epithelial cells (the type of cells lining surfaces in
your body, such as the inside of your eyes, your
blood vessels, and your skin - the most abundant
cell type) can crawl across a surface using
lamellipodia. A lamellipodium is a sheet-like
extension of the cell across the surface, filled with
actin fibers, shown in red in the image on the right.
Lamellipodia grow by actin polymerization, and are
part of a continuous dynamical process of
cytoskeletal construction and disassembly. This
process is responsible for creating forces in the cell,
which in turn are used to pull the cell forward. To do
so, they need to make physical connection with the
surface underneath, which they do through focal
contacts.
In this project, youʼll model lamellipodium dynamics
and cell motility using a course-grained description in
which the lamellipodium is chopped up in parts
roughly equal in size to the region of a focal contact so much smaller than the lamellipodium itself, but
much larger than an actin filament. Using a basic set
of rules for the interaction of these parts, youʼll study
their dynamics, as they stochastically explore the
space around the cell. To do so, youʼll perform
molecular dynamics simulations, in which you
calculate the forces on each part, and use those to
calculate their instantaneous velocities and
displacements. Youʼll also calculate stresses
generated by the lamellipodium, and use those to
match your simulations to experimental
observations.
Migrating epithelial mouse cell with a
lamellipodium extension. The leading
edge is the red curve, rich in actin, one
of the cytoskeletal fibers in the cell. On
the trailing edge, a protein called cofilin
(shown in green) disassembles the actin.
The blob-like object near the read is the
cell nucleus.
image source: http://
www.bpod.mrc.ac.uk/archive/2012/1/17