Active tuning of synaptic patterns enhances affinity discrimination

Immune cells learn about their antigenic targets using tactile sense: during recognition, a highly organized yet dynamic motif, named immunological synapse, forms between immune cells and antigen-presenting cells (APCs). Via synapses, immune cells selectively extract recognized antigen from APCs by applying mechanical pulling forces generated by the contractile cytoskeleton. Curiously, depending on its stage of development, an immune cell exhibits distinct synaptic patterns which appear to strongly impact its capacity of distinguishing antigen affinities. While complete phase separation between receptor-ligand complexes and bound adhesion molecules observed in naïve (antigen-inexperienced) cells can be captured by existing models, how and why maturing cells maintain a multifocal pattern characteristic of arrested phase separation remains an unsolved puzzle. In this talk, I introduce a statistical-mechanical model to show that normal cytoskeletal forces can tune the degree of phase separation and thereby actively control the transition between distinct patterns. What is more, we find that normal forces coupled to lateral organization of receptors provide a robust grading scheme that allows efficient and broad affinity discrimination essential for proper immune function.