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11 - A Molecular Perspective on Mechanotransduction in Focal Adhesions

Published online by Cambridge University Press:  05 July 2014

By
Seung E. Lee ,
Roger D. Kamm  and
Mohammad R. K. Mofrad
Edited by
Mohammad R. K. Mofrad  and
Roger D. Kamm
Seung E. Lee
Affiliation:
University of California, Berkeley
Roger D. Kamm
Affiliation:
Massachusetts Institute of Technology
Mohammad R. K. Mofrad
Affiliation:
University of California, Berkeley
Mohammad R. K. Mofrad
Affiliation:
University of California, Berkeley
Roger D. Kamm
Affiliation:
Massachusetts Institute of Technology
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Summary

Mechanotransduction and Focal Adhesions

Living cells respond to mechanical stimulation in a variety of ways that shape their phenotype in health and disease. Such a mechanosensing character is essential for cells to probe their environment and respond accordingly to their fate of cell growth, differentiation, or death. Although the biochemical signaling pathways activated by mechanical stimuli have been extensively studied, little is known of the basic underlying mechanisms. As discussed throughout this book, several mechanisms of mechanotransduction have been proposed. It is conceivable that the mechanical signal may be transduced into a chemical signal through protein activation, leading to the upregulation of intracellular signaling proteins. Alternatively, the forces may be transmitted via individual proteins either at the site of cell adhesion to its surroundings or within the stress-bearing members of the cytoskeleton and can cause conformational changes that alter their binding affinity to other intracellular molecules. This altered equilibrium state can subsequently initiate a biochemical signaling cascade or produce more immediate and local structural changes; see reviews [1–4].

One extensively studied example of mechanotransduction is force regulation of the focal adhesion assembly. Focal adhesions have important cellular functions, and their study can provide useful insight into understanding mechanotransduction pathways. Many studies have looked into the force response of focal adhesions with the aim of understanding their mechanisms and implications. The focus of this chapter will be on the direct mechanical response of focal adhesions at the cellular and molecular levels. In the remainder of this section, the role of focal adhesions and their maturation stages are discussed. In the following section, experimental studies on force regulation of focal adhesions are described. Then, the numerical works on the effect of force on adhesion proteins and their molecular mechanisms are examined. Finally, future outlook and perspectives are presented in the last section.

Type
Chapter
Information
Cellular Mechanotransduction
Diverse Perspectives from Molecules to Tissues
 , pp. 250 - 268
Publisher: Cambridge University Press
Print publication year: 2009

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