Mechanosensing in the immune response

Abstract

Cells have a remarkable ability to sense and respond to the mechanical properties of their environment. Mechanosensing is essential for many phenomena, ranging from cell movements and tissue rearrangements to cell differentiation and the immune response. Cells of the immune system get activated when membrane receptors bind to cognate antigen on the surface of antigen presenting cells. Both T and B lymphocyte signaling has been shown to be responsive to physical forces and mechanical cues. Cytoskeletal forces exerted by cells likely mediate this mechanical modulation. Here, we discuss recent advances in the field of immune cell mechanobiology at the molecular and cellular scale.

Keywords: Actin; Cytoskeleton; Forces; Immune cells; Mechanosensing; T cell receptor.

Figure 1. Cytoskeletal forces during immune cell activation

(a) Schematic diagram of a T cell spreading on the surface of an APC. The contact zone shows spatiotemporal organization of actin into Arp2/3 mediated branched networks and formin-mediated actin arcs. MT emanate from the centrosome. The insets depict conformational changes resulting from the application of actomyosin forces on TCR microclusters (left) and integrin receptors (right). One of many possible conformational changes in the TCR is shown. Cartoons of (b) a cell on PDMS microposts showing deflection of posts resulting from cellular forces, (c) a cell on a PA gel depicting movement of embedded beads as the cell exerts traction forces. The measured displacement field u(x) and the traction stress field, f(x) are related by the integral equation in the figure, with G(x–y) is the Boussinesq Green function, (d) a cell on a glass substrate with DNA-hairpin based tension sensors. The flurophore (red sphere) is near the quencher (black sphere) when the ligand attached to the hairpin is free. Ligand binding and subsequent force application moves fluorophore away from the quencher.