Speaker
Description
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. While the mechanobiology of the TCR at the molecular level is increasingly well documented, its link to cell-scale response is poorly understood. We show that the response of T cells, quantified in terms of their spreading behaviour, is biphasic with substrate stiffness when mediated through TCRs [1]. However, when the ligands of the T cell integrins are additionally involved, the cellular response becomes monotonic [1]. This ligand-specific mechanosensing is effected through an actin-polymerization–dependent mechanism [2]. Based on a mesoscale model, this unusual 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 [1,2], whose mechanics was be probed by tether pulling [3]. This may provide a general mechanism for immune cells to discriminate mechanosensitive bonds.
[1] . A. Wahl, C. Dinet, P. Dillard, A. Nassereddine, P-H. Puech, L. Limozin, and K. Sengupta, Proc. Nat. Acad. Sci. 116, 5908 (2019)
[2] P. Dillard, R. Varma, L. Limozin and K. Sengupta., Biophys J. 107, 2629 (2014).
[3] F. Manca , G. Eich , O. N'Dao , L. Normand , K. Sengupta , L. Limozin , P-H. Puech.
