CUED Publications database

An analysis of the cooperative mechano-sensitive feedback between intracellular signaling, focal adhesion development, and stress fiber contractility

Pathak, A and McMeeking, RM and Evans, AG and Deshpande, VS (2011) An analysis of the cooperative mechano-sensitive feedback between intracellular signaling, focal adhesion development, and stress fiber contractility. Journal of Applied Mechanics, Transactions ASME, 78. ISSN 0021-8936

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Abstract

Cells communicate with their external environment via focal adhesions and generate activation signals that in turn trigger the activity of the intracellular contractile machinery. These signals can be triggered by mechanical loading that gives rise to a cooperative feedback loop among signaling, focal adhesion formation, and cytoskeletal contractility, which in turn equilibrates with the applied mechanical loads. We devise a signaling model that couples stress fiber contractility and mechano-sensitive focal adhesion models to complete this above mentioned feedback loop. The signaling model is based on a biochemical pathway where IP3 molecules are generated when focal adhesions grow. These IP3 molecules diffuse through the cytosol leading to the opening of ion channels that disgorge Ca2+ from the endoplasmic reticulum leading to the activation of the actin/myosin contractile machinery. A simple numerical example is presented where a one-dimensional cell adhered to a rigid substrate is pulled at one end, and the evolution of the stress fiber activation signal, stress fiber concentrations, and focal adhesion distributions are investigated. We demonstrate that while it is sufficient to approximate the activation signal as spatially uniform due to the rapid diffusion of the IP3 through the cytosol, the level of the activation signal is sensitive to the rate of application of the mechanical loads. This suggests that ad hoc signaling models may not be able to capture the mechanical response of cells to a wide range of mechanical loading events. © 2011 American Society of Mechanical Engineers.

Item Type: Article
Uncontrolled Keywords: actin/myosin contractility cell signaling focal adhesions mechano-sensitivity
Subjects: UNSPECIFIED
Divisions: Div C > Materials Engineering
Depositing User: Cron Job
Date Deposited: 07 Mar 2014 11:26
Last Modified: 27 Nov 2014 19:19
DOI: 10.1115/1.4003705