Figure 7.

A bistable mechanism of cell adhesion spatial regulation explains integrin control of T cell flow mechanotaxis. On pure substrates of ICAM-1 or VCAM-1, the T cell population has homogeneous phenotypes with an opposite orientation on ICAM-1 and VCAM-1. On mixed substrates of ICAM-1 or VCAM-1, T cells distribute in two populations with opposite orientations and characteristics similar to phenotypes on pure substrates. Decisions of orientation on mixed substrates are controlled by the expression level of integrins LFA-1 and VLA-4 via a bistable polarization of cell adhesion; a higher LFA-1 expression leads to a LFA-1-dominated adhesion of cell front (very similar to upstream crawling cells on ICAM-1), whereas a higher expression of VLA-4 leads to adhesion of cell rear and center (very similar to downstream crawling cells on VCAM-1). Inhibiting cross talk of LFA-1 toward VLA-4 reinforces adhesion polarization toward cell front, which favors wind vane mechanism and upstream phenotype. Activating cross talk of VLA-4 toward LFA-1 reinforces the adhesion of cell uropod, which hampers the wind vane mechanism and favors the downstream phenotype. To see this figure in color, go online.