Constructing a motile cell : how extrinsic information and intrinsic self-organization coordinate the mechanics of cellular behavior

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Abstract/Contents

Abstract
The actin-based crawling motility of eukaryotic cells is a vital example of emergent cellular behavior arising from the mechanical output of thousands to millions of individual chemical reactions occurring every second. In this work, I describe a set of experimental and analytical results that seek to reveal the underlying organization and operations of this micron sized biological machine. We found that the morphology of crawling cells is quantitatively dictated by the cytoskeletal elements that produce motility. Each cell is unique in its organization and behavior, and across a population of cells this variation could largely be reduced to a single dimension. Globally perturbing the biochemical reaction rates that drive motility with changes in temperature forced individual cells out of their steady state behavior along this same single dimension of variation. In addition individual cells fluctuated harmonically around their steady state behavior, suggesting a mechanical oscillator arising from the coupling of the processes of actin meshwork assembly and disassembly. Flickers of elevated intracellular concentration of the canonical secondary messenger calcium were seen, but these calcium flickers were not required for cell motion nor were they correlated with any measured change in cell behavior. The orientation of motion, similar to the rate of motion, is directly coupled to the cytoskeletal organization and cellular shape. To change their direction of migration, cells develop asymmetries in the interwoven actions of myosin contractility and adhesion to the substrate at the rear of the cell creating asymmetric centripetal actin flow. This system of controlling orientation was responsive to external cues from electric fields secondary to electrophoretic redistribution of charged membrane components extending into the extracellular space.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2013
Issuance monographic
Language English

Creators/Contributors

Associated with Allen, Greg Maness
Associated with Stanford University, Department of Biochemistry.
Primary advisor Theriot, Julie
Thesis advisor Theriot, Julie
Thesis advisor Chu, Gilbert
Thesis advisor Straight, Aaron, 1966-
Advisor Chu, Gilbert
Advisor Straight, Aaron, 1966-

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Greg Maness Allen.
Note Submitted to the Department of Biochemistry.
Thesis Thesis (Ph.D.)--Stanford University, 2013.
Location electronic resource

Access conditions

Copyright
© 2013 by Greg Maness Allen
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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