Mechanisms Controlling Cell Size and Shape during Isotropic Cell Spreading

Yuguang Xiong, Padmini Rangamani, Marc-Antoine Fardin, Azi Lipshtat, Benjamin Dubin-Thaler, Olivier Rossier, Michael P. Sheetz, Ravi Iyengar
Biophysical Journal. 2010-05-01; 98(10): 2136-2146
DOI: 10.1016/j.bpj.2010.01.059

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1. Biophys J. 2010 May 19;98(10):2136-46. doi: 10.1016/j.bpj.2010.01.059.

Mechanisms controlling cell size and shape during isotropic cell spreading.

Xiong Y(1), Rangamani P, Fardin MA, Lipshtat A, Dubin-Thaler B, Rossier O, Sheetz
MP, Iyengar R.

Author information:
(1)Department of Pharmacology and Systems Therapeutics, Mount Sinai School of
Medicine, New York, New York, USA.

Erratum in
Biophys J. 2010 Jul 21;99(2):695.

Cell motility is important for many developmental and physiological processes.
Motility arises from interactions between physical forces at the cell surface
membrane and the biochemical reactions that control the actin cytoskeleton. To
computationally analyze how these factors interact, we built a three-dimensional
stochastic model of the experimentally observed isotropic spreading phase of
mammalian fibroblasts. The multiscale model is composed at the microscopic levels
of three actin filament remodeling reactions that occur stochastically in space
and time, and these reactions are regulated by the membrane forces due to
membrane surface resistance (load) and bending energy. The macroscopic output of
the model (isotropic spreading of the whole cell) occurs due to the movement of
the leading edge, resulting solely from membrane force-constrained biochemical
reactions. Numerical simulations indicate that our model qualitatively captures
the experimentally observed isotropic cell-spreading behavior. The model predicts
that increasing the capping protein concentration will lead to a proportional
decrease in the spread radius of the cell. This prediction was experimentally
confirmed with the use of Cytochalasin D, which caps growing actin filaments.
Similarly, the predicted effect of actin monomer concentration was experimentally
verified by using Latrunculin A. Parameter variation analyses indicate that
membrane physical forces control cell shape during spreading, whereas the
biochemical reactions underlying actin cytoskeleton dynamics control cell size
(i.e., the rate of spreading). Thus, during cell spreading, a balance between the
biochemical and biophysical properties determines the cell size and shape. These
mechanistic insights can provide a format for understanding how force and
chemical signals together modulate cellular regulatory networks to control cell

Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights

DOI: 10.1016/j.bpj.2010.01.059
PMCID: PMC2872297
PMID: 20483321 [Indexed for MEDLINE]

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