Signaling Network Triggers and Membrane Physical Properties Control the Actin Cytoskeleton-Driven Isotropic Phase of Cell Spreading
Biophysical Journal. 2011-02-01; 100(4): 845-857
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1. Biophys J. 2011 Feb 16;100(4):845-57. doi: 10.1016/j.bpj.2010.12.3732.
Signaling network triggers and membrane physical properties control the actin
cytoskeleton-driven isotropic phase of cell spreading.
Rangamani P(1), Fardin MA, Xiong Y, Lipshtat A, Rossier O, Sheetz MP, Iyengar R.
(1)Department of Pharmacology and Systems Therapeutics, Mount Sinai School of
Medicine, New York, New York, USA.
Cell spreading is regulated by signaling from the integrin receptors that
activate intracellular signaling pathways to control actin filament regulatory
proteins. We developed a hybrid model of whole-cell spreading in which we modeled
the integrin signaling network as ordinary differential equations in multiple
compartments, and cell spreading as a three-dimensional stochastic model. The
computed activity of the signaling network, represented as time-dependent
activity levels of the actin filament regulatory proteins, is used to drive the
filament dynamics. We analyzed the hybrid model to understand the role of
signaling during the isotropic phase of fibroblasts spreading on
fibronectin-coated surfaces. Simulations showed that the isotropic phase of
spreading depends on integrin signaling to initiate spreading but not to maintain
the spreading dynamics. Simulations predicted that signal flow in the absence of
Cdc42 or WASP would reduce the spreading rate but would not affect the shape
evolution of the spreading cell. These predictions were verified experimentally.
Computational analyses showed that the rate of spreading and the evolution of
cell shape are largely controlled by the membrane surface load and membrane
bending rigidity, and changing information flow through the integrin signaling
network has little effect. Overall, the plasma membrane acts as a damper such
that only ∼5% of the actin dynamics capability is needed for isotropic spreading.
Thus, the biophysical properties of the plasma membrane can condense varying
levels of signaling network activities into a single cohesive macroscopic
Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights
PMID: 21320428 [Indexed for MEDLINE]