title: Confinement-optimized three-dimensional T cell amoeboid motility is modulated via myosin IIA-regulated adhesions.
abstract: During trafficking through tissues, T cells fine-tune their motility to balance the extent and duration of cell-surface contacts versus the need to traverse an entire organ. Here we show that in vivo, myosin IIA-deficient T cells had a triad of defects, including overadherence to high-endothelial venules, less interstitial migration and inefficient completion of recirculation through lymph nodes. Spatiotemporal analysis of three-dimensional motility in microchannels showed that the degree of confinement and myosin IIA function, rather than integrin adhesion (as proposed by the haptokinetic model), optimized motility rate. This motility occurred via a myosin IIA-dependent rapid 'walking' mode with multiple small and simultaneous adhesions to the substrate, which prevented spurious and prolonged adhesions. Adhesion discrimination provided by myosin IIA is thus necessary for the optimization of motility through complex tissues.
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, California, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Jacobelli
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Friedman
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Conti
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Lennon-Dumenil
authors.forename: Matthieu
authors.initials: M
authors.lastname: Piel
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Sorensen
authors.forename: Robert S
authors.initials: RS
authors.lastname: Adelstein
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement; D005260:Female; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024507:Nonmuscle Myosin Type IIA / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D024507:Nonmuscle Myosin Type IIA