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To fulfill their killing functions, cytotoxic T lymphocytes (CTLs) need tomigrate to search for their target cells in complex biologicalmicroenvironments, a key component of which is extracellular matrix (ECM). Themechanisms underlying CTL's navigation are not well understood so far. Here weuse a collagen assay as a model for the ECM and analyze the migrationtrajectories of primary human CTLs in collagen matrices with differentconcentrations. We observe different migration patterns for individual T cells.Three different motility types can be distinguished: slow, fast and mixedmotilities. Slow CTLs remain nearly stationary within the collagen matrix andshow slightly anti-persistent motility, while the fast ones move quickly andpersistent (i.e. with not too large turning angles). The dynamics of the mixedtype consists of periods of slow and fast motions; both states are persistent,but they have different persistencies. The dynamics can be well described by atwo-state persistent random walk model. We extract the parameters of the modelby analyzing experimental data. The mean square displacements predicted by themodel and those measured experimentally are in very good agreement, without anyfitting parameter. Potential reasons for the observed two-state motility arediscussed. T cells dig the collagen during their migration and form channels,which facilitate the movement of other CTLs in the collagen network.

Migration of Cytotoxic T Lymphocytes in 3D Collagen Matrices