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Spatiotemporal organization, regulation and function of traction during neutrophil chemotaxis

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Title: Spatiotemporal organization, regulation and function of traction during neutrophil chemotaxis
Author(s): Shin, Myung Eun
Director of Research: Wang, Fei
Doctoral Committee Chair(s): Belmont, Andrew S.
Doctoral Committee Member(s): Wang, Fei; Chen, Jie; Newmark, Phillip A.; Xiang, Yang
Department / Program: Cell & Developmental Biology
Discipline: Cell and Developmental Biology
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: Ph.D.
Genre: Dissertation
Subject(s): Neutrophil Chemotaxis Traction Myosin-Light-Chain Kinase Myosin Type II Cell Adhesion Cell Motility Mechanotransduction
Abstract: Despite recent advances in our understanding of biochemical regulation of neutrophil chemotaxis, little is known about how mechanical factors control neutrophils’ persistent polarity and rapid motility. Here, by using a human neutrophil-like cell line and human primary neutrophils, we describe a dynamic spatiotemporal pattern of tractions in neutrophils during chemotaxis. Tractions are located at both the leading and the trailing edge of neutrophils, where they oscillate with a defined periodicity. Interestingly, traction oscillations at the leading and the trailing edge are out of phase with the tractions at the front leading those at the back, suggesting a temporal mechanism that coordinates leading edge and trailing edge activities. The magnitude and periodicity of tractions depend upon the activity of non-muscle myosin IIA. Specifically, traction development at the leading edge requires myosin light chain kinase (MLCK)-mediated myosin II contractility and is necessary for α5β1-integrin activation and leading edge adhesion. Localized myosin II activation induced by spatially activated small GTPase Rho and its downstream kinase p160-ROCK, as previously reported, leads to contraction of actin-myosin II complexes at the trailing edge, causing it to de-adhere. Our data identify a key biomechanical mechanism for persistent cell polarity and motility.
Issue Date: 2012-02-01
URI: http://hdl.handle.net/2142/29509
Rights Information: Copyright 2011 Myung Eun Shin
Date Available in IDEALS: 2014-02-01
Date Deposited: 2011-12
 

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