Amoeboid T-cell migration, physical cell-fiber interaction, and contact guidance within 3D collagen matrix in the absence or presence of protease inhibitor cocktail. (A) Untreated and (B) protease inhibitor cocktail–teated calcein-stained T cells. Crawling, alignment along fiber strands (black arrowheads) and formation of constriction rings (white arrowheads). Image sequences (i-vi) represent as a time series 8 (A) and 3 (B) minutes of observation time. (C) T-cell alignment in parallel to matrix fibers (white arrowheads) upon forward migration (black arrow). (D) Change in migration direction. Angle turns along the cellular length axis (cyan arrow, small inset) and physical confinement of the cell body and uropod along guiding collagen fibers (white arrowheads), reflecting the direction change. Bars, 5 μm.