Biphasic mechanosensitivity of T cell receptor-mediated spreading of lymphocytes

A. Wahl, C. Dinet, P. Dillard, A. Nassereddine, P-H. Puech, L. Limozin & K. SenguptA. PNAS 2019 116 (13) 5908-5913.
Usually, cell spreading goes up monotonically with environmental stiffness as is the case here for the red curve (T cell adhesion mediated by TCRs and integrins). We show that this relation may, under special circumstances, also be biphasic as seen above for the blue curve (T cell adhesion mediated by TCRs alone).

The ability of a T cell to explore environmental mechanical cues, through bonds formed by its special receptors called T cell receptors (TCRs), is crucial for the first steps of immune recognition. Here we show that the response of T cells, quantified in terms of their spreading behavior, is biphasic with substrate stiffness when mediated through TCRs. However, when the ligands of the T cell integrins are additionally involved, the cellular response becomes monotonic. Based on a mesoscale model, this ligand-specific response can be attributed to differences in force sensitivity and effective stiffness of the link formed between the ligand/receptor pairs and the actin cytoskeleton. This may provide a general mechanism for immune cells to discriminate mechanosensitive bonds.