2006 APS March Meeting
Monday–Friday, March 13–17, 2006;
Baltimore, MD
Session U26: Focus Session: Cytoskeletal Dynamics
8:00 AM–11:00 AM,
Thursday, March 16, 2006
Baltimore Convention Center
Room: 323
Sponsoring
Units:
GSNP DBP DPOLY
Chair: Christina Marchetti, Syracuse University
Abstract ID: BAPS.2006.MAR.U26.7
Abstract: U26.00007 : The mechanics of cell protrusion*
9:12 AM–9:48 AM
Preview Abstract
Abstract
Author:
Gaudenz Danuser
(The Scripps Research Institute)
The protrusion of the cell edge is the first step in a cycle of molecular
processes that drive cell movements during development, immune responses,
wound healing and many other physiological functions. It is also the
earliest pathological event observed during metastasis of cancer. Textbook
models associate protrusion with the assembly of an actin polymer network
subadjacent to the cell plasma membrane. However, for this process to be
transformed into edge advancement, polymerization-induced forces need to be
balanced by adhesion complexes that link the actin network to the
extracellular domain. Also, the effectiveness of network assembly in
mediating forward movement of the cell edge depends on how contraction
forces pull the network in the cell front retrogradly towards the cell
center. Thus, what is observed in a microscope as cell protrusion reflects
the kinematic output of at least three space- and time-modulated mechanisms
of force generation. The coordination of these machineries is thought to be
regulated by a complex network of mechano-chemical signals. Our goal is to
establish the contributions of each those mechanisms and their control by
reconstructing the spatiotemporal distribution of intracellular forces via
inverse dynamics and molecular intervention with the relevant signalling
pathways. To this end, we have developed quantitative Fluorescent Speckle
Microscopy (qFSM) which provides high-resolution spatiotemporal measurements
of actin network deformation and material properties in migrating cells. In
addition, qFSM delivers maps of cytoskeleton assembly and disassembly, so
that we can infer the plasticity of the material in situ. Together, this
data allows us to deduce intracellular force distributions from the
constitutive laws of strain and stress in the actin polymer network. Using
this approach we discovered that unperturbed cells protrude in a dynamic
steady state where periodic patterns of network assembly, adhesion
formation, and cytoskeleton transport are tightly connected to protrusion
waves. We exploited the sub-cellular heterogeneity of these patterns to
identify the causality and timing between dynamic events in the actin
network, leading towards a first integral view of the mechano-chemical
process interaction in the protrusion machinery.
*NIH R01 GM67230, U54 RR22230
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2006.MAR.U26.7