Spatiotemporal organization, regulation, and functions of tractions 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, using a human neutrophil-like cell line and human primary neutrophils, we describe a dynamic spatiotemporal pattern of tractions 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 on the activity of nonmuscle myosin IIA. Specifically, traction development at the leading edge requires myosin light chain kinase-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.
Shin
Myung Eun
ME
Department of Cell and Developmental Biology and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
He
Yuan
Y
Li
Dong
D
Na
Sungsoo
S
Chowdhury
Farhan
F
Poh
Yeh-Chuin
YC
Collin
Olivier
O
Su
Pei
P
de Lanerolle
Primal
P
Schwartz
Martin A
MA
Wang
Ning
N
Wang
Fei
F
D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism
D039081:Integrin alpha5beta1; D009219:Myosin-Light-Chain Kinase; D024462:Myosin Type II