Spatiotemporal organization, regulation and functions of tractions during neutrophil chemotaxis
Shin, Myung Eun
de Lanerolle, Primal
Schwartz, Martin A.
PublisherAmerican Society of Hematology
MetadataShow full item record
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 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 51- 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.