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10 - Microtubule Bending and Breaking in Cellular Mechanotransduction

Published online by Cambridge University Press:  05 July 2014

Andrew D. Bicek
Affiliation:
University of Minnesota
Dominique Seetapun
Affiliation:
University of Minnesota
David J. Odde
Affiliation:
University of Minnesota
Mohammad R. K. Mofrad
Affiliation:
University of California, Berkeley
Roger D. Kamm
Affiliation:
Massachusetts Institute of Technology
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Summary

Introduction

Cellular mechanotransduction is the mechanism by which living cells respond to mechanical signals from their environment. As early as 1892, Julius Wolff described the ability of bone to be deposited and resorbed in accordance with the mechanical stresses placed upon it, implying that the bone must have some internal mechanical stress or strain sensors (Huiskes and Verdonschot, 1997; Roesler, 1987; Wolff, 1892). More recently, investigating the precise biochemical mechanisms by which a direct mechanical stimulus is converted into a cellular response has become an area of interest, and the macro-scale effects of mechanotransduction, such as the alignment of load-bearing components, are now widely recognized. For example, the extracellular matrix protein, collagen, is organized into a hierarchy of fibrillar structures by tenocytes to form a tendon that functionally transmits mechanical tension (Kastelic et al., 1978). Additionally, vascular endothelial cells have been observed to align and alter their morphology in response to an applied fluid shear stress (Levesque and Nerem, 1985). In another example of cells sensing a mechanical stimulus, neuronal cells are capable of responding directly to a tensile force through neurite initiation and extension, a phenomenon termed “towed growth” (Bray, 1984; Fass and Odde, 2003; Fischer et al., 2005; Heidemann and Buxbaum, 1990; Pfister et al., 2004). Since individual cells are capable of responding directly to an applied force via secreting, organizing, and remodeling the extracellular matrix, or through morphological and gene expression changes, mechanotransduction is presumably controlled and integrated into a response at the cellular level.

Perhaps the best documentation of cellular mechanotransduction is the role of mechanically gated ion channels in hearing (Hudspeth, 1989). The stereocilia of the auditory hair cells vibrate and bend with incoming sound waves. As the stereocilia bend, a linker protein filament is tensed between two adjacent cilia and the tension generated opens a mechanically gated ion channel. Opening of the ion channel causes an influx of positive charges that depolarize the hair cell and lead to an electrical signal that the brain interprets as sound. While this is a clear example of a mechanotransduction event, it is also clear that mechanically gated ion channels are not the sole mechanism for mechanotransduction in every cell. Other structures within the cell therefore need to be identified and investigated for their mechanosensory features, with the cytoskeleton being a leading candidate.

Type
Chapter
Information
Cellular Mechanotransduction
Diverse Perspectives from Molecules to Tissues
, pp. 234 - 249
Publisher: Cambridge University Press
Print publication year: 2009

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