CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize β1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion

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Abstract
Cell migration may depend on integrin‐mediated adhesion to and deadhesion from extracellular matrix ligands. This concept, however, has not yet been confirmed for T lymphocytes migrating in three‐dimensional extracellular matrices. We investigated receptor involvement in T cell migration combining a three‐dimensional collagen matrix model with time‐lapse videomicroscopy, computer‐assisted cell tracking and confocal microscopy. In collagen lattices, the migration of CD4+ T cells (1) involved interactions with collagen fibers at the leading edge and uropod likewise, (2) occurred independently of the co‐clustering of β1, β2, or β3 integrins with F‐actin, focal adhesion kinase, and phosphotyrosine at interactions with collagen fibers, (3) was counteracted by high‐affinity β1 integrin binding induced by antibody TS2/16; however, (4) the migration could not be blocked by a combination of adhesion‐perturbing anti‐β1, ‐β2, ‐β3, and αv integrin antibodies. Integrin blocking neither affected cell polarization, interaction with fibers, β1 integrin distribution, migration velocity, path structure, nor the number of locomoting cells in spontaneously migrating or concanavalin A‐activated cells. Hence, T lymphocytes migrating in three‐dimensional collagen matrices may utilize highly transient interactions with collagen fibers of low adhesivity, thereby differing from focal adhesion‐dependent migration strategies employed by other cells.