Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 95, Issue 6, Pages 993-1004Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0913478
Keywords
integrins; migration; mechanosensing; biophysics
Categories
Funding
- U.S. National Institutes of Health [GM-066194, AI-079582]
- U.S. Department of Education
- Natural Sciences and Engineering Research Council of Canada
- Rhode Island Hospital
- Direct For Mathematical & Physical Scien
- Division Of Physics [1058375] Funding Source: National Science Foundation
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A direct consequence of cellular movement and navigation, migration incorporates elements of speed, direction, and persistence of motion. Current techniques to parameterize the trajectory of a chemotaxing cell most commonly pair migration speed with some measure of persistence by calculating MSD, RMS speed, TAD, and/or CI. We address inherent limitations in TAD and CI for comparative analysis by introducing two new analytical tools to quantify persistence: directionality index and directionality time. With the use of these tools, we show that the mechanical properties of the underlying substrate contribute significantly to the regulation of human neutrophil chemotaxis toward fMLP on Fgn-, Col-, and Fn-coated gels of varying elasticity. The beta 1-integrin ligand Col demonstrated mechanosensitive speed. In contrast, beta(2)-integrin ligand Fgn supported mechanosensitive persistence. Fn, recognized by beta(1) and beta(2) integrins, mechanoregulated speed and persistence. Blocking beta(2) integrins of cells migrating on Fn identified an underlying beta(2)-integrin-directed modulation of persistence. These data demonstrate that individual components of the neutrophil chemotactic response show integrin dependence and are finely tunable with different ligand, mechanotactic, and chemotactic cues, underscoring the need for sensitive analytical methods.
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