Spatiotemporal organization, regulation and function of traction during neutrophil chemotaxis

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Cell and Developmental Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2012

Author dc:creator

• Shin, Myung Eun

Contributors dc:contributor

• Wang, Fei
• Belmont, Andrew S.
• Chen, Jie
• Newmark, Phillip A.
• Xiang, Yang

• Neutrophil Chemotaxis
• Traction
• Myosin-Light-Chain Kinase
• Myosin Type II
• Cell Adhesion
• Cell Motility
• Mechanotransduction

Statement dc:rights

• Copyright 2011 Myung Eun Shin

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/29509

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/29509