Spatiotemporal organization, regulation, and functions of tractions during neutrophil chemotaxis

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, 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 ␣5␤1-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. (Blood. 2010;116(17):3297-3310)

Shape and Area of Keratocytes Are Related to the Distribution and Magnitude of Their Traction Forces

“…The physiological significance of the positive relationship between the ventral area and the force of keratocytes is also unknown. In most of migrating cell types, the traction forces at the rear end are the result of contraction of the rear, which is indispensable for advance (Iwadate and Yumura, 2008a;Munevar et al, 2001aMunevar et al, , 2001bShin et al, 2010). The positive relationship may be necessary for the same migration velocity in different sizes of the cell (Fig.…”

Cell-stiffness-induced mechanosignaling – a key driver of leukocyte transendothelial migration

“…tugging) to sense and respond to substrate stiffness (Califano and Reinhart-King, 2010;Plotnikov et al, 2012;Plotnikov and Waterman, 2013). Neutrophils show greater tugging on stiffer surfaces that are coated with extracellular matrix (ECM) proteins or ECs (Oakes et al, 2009;Shin et al, 2010;Stroka et al, 2013). This promotes leukocyte adhesion, spreading and TEM.…”

“…The response of a leukocyte to EC stiffness by generating actomyosin-based forces is regulated in a spatiotemporal manner, as shown by traction force microscopy with human neutrophils (Shin et al, 2010). During TEM, large traction forces are generated in the uropod, the trailing end of a migrating leukocyte (Oakes et al, 2009;Shin et al, 2010;Stroka et al, 2013).…”

“…During TEM, large traction forces are generated in the uropod, the trailing end of a migrating leukocyte (Oakes et al, 2009;Shin et al, 2010;Stroka et al, 2013). Uropod retraction is required for efficient TEM of neutrophils, monocytes and T cells in vitro and in vivo (Hyun et al, 2012;Stroka et al, 2013).…”

Hybrid mechanosensing system to generate the polarity needed for migration in fish keratocytes

“…[11][12][13] Interestingly, even in media containing a uniform concentration of fMLP, HL-60 cells localize actin filaments to a portion of the cell and myosin IIA or RhoA to the opposite side to enable migration. 14,15 Dictyostelium cells also can localize phosphatidylinositol 3,4,5-trisphosphate, which plays a role in the generation of migrating polarity, at a portion of the cell even in media containing a uniform concentration of cAMP [16][17][18] and migrate while regarding the portion as front. These observations suggest that migrating cells can generate their own polarity and migrate in a chosen direction, even in the absence of a concentration gradient of an attractive substance.…”