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Membrane-Binding/Modification Model of Signaling Protein Activation and Analysis of Its Control by Cell Morphology

Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695

Correspondence: Address reprint requests and inquiries to Jason M. Haugh, Tel.: 919-513-3851; Fax: 919-515-3465; E-mail: jason_haugh{at}ncsu.edu.

A mechanism for cell shape control of intracellular signal transduction, whereby the average concentration of activated proteins in the cytosol increases as the height of the cell decreases, has been described recently. An important modification of this analysis is offered, recognizing that signaling proteins are not only activated at the plasma membrane but must first form complexes with signaling molecules that reside there, such as receptors and lipids. With these more realistic boundary conditions, it is shown that the region of parameter space where cell shape amplifies the average cytosolic activity is greatly expanded. Moreover, this model allows for amplification of the activated protein bound at the membrane, which is considered more relevant for certain, spatially driven signaling processes in cell migration.