Mechanical activity enables patterning and discrimination at the immune synapse

TL;DR

This paper presents a minimal continuum model demonstrating how active mechanical forces, such as cortical flows and pulling, regulate pattern formation and antigen discrimination at immune synapses, emphasizing the role of cytoskeletal dynamics.

Contribution

It introduces a coupled model of receptor kinetics, membrane deformation, and cytoskeletal forces to explain active mechanical control in immune synapse patterning and discrimination.

Findings

Contractile cortical flows stabilize receptor clusters.

Active pulling accelerates cluster dissolution.

Mechanical forces modulate discrimination sensitivity.

Abstract

Immune cells recognize and discriminate antigens through immunological synapses - dynamic intercellular junctions exhibiting highly organized receptor-ligand patterns. While much work has focused on molecular kinetics and passive mechanisms of pattern formation, the role of active mechanical control in patterning and discrimination remains underexplored. We develop a minimal continuum model coupling receptor binding kinetics, membrane deformation, and cytoskeletal forces, with elastohydrodynamic flow in the synaptic cleft. Numerical simulations and scaling analysis reveal that contractile cortical flows arrest coarsening and stabilize long-lived multifocal clusters, whereas active pulling accelerates cluster dissolution and elevates background receptor binding. Nonequilibrium mechanical forces enable adaptive control over the speed, sensitivity, and dynamic range of affinity discrimination in a pattern-dependent manner. Our results highlight how immune cells exploit cytoskeletal remodeling to robustly regulate antigen recognition through synaptic patterning.