Immune cells use active tugging forces to distinguish affinity and accelerate evolution

TL;DR

This paper proposes that immune cells use active mechanical forces to distinguish antigen affinity and accelerate evolution, revealing how physical forces influence immune adaptation and selection.

Contribution

It introduces a theoretical framework linking cellular tug-of-war forces to evolutionary fitness, unifying mechanosensing with affinity discrimination in immune cells.

Findings

Force-enhanced discrimination improves selection accuracy.

Active pulling accelerates immune cell evolution.

Optimal force range balances adaptation speed and population survival.

Abstract

Cells are known to exert forces to sense their physical surroundings for guidance of motion and fate decisions. Here, we propose that cells might do mechanical work to drive their own evolution, taking inspiration from the adaptive immune system. Growing evidence indicates that immune B cells - capable of rapid Darwinian evolution - use cytoskeletal forces to actively extract antigen from other cells' surface. To elucidate the evolutionary significance of force usage, we develop a theory of tug-of-war antigen extraction that maps receptor binding characteristics to clonal reproductive fitness, revealing physical determinants of selection strength. This framework unifies mechanosensing and affinity-discrimination capabilities of evolving cells: pulling against stiff antigen tethers enhances discrimination stringency at the expense of absolute extraction. As a consequence, active force usage can accelerate adaptation but may also cause extinction of cell populations, resulting in an optimal range of pulling strength that matches molecular rupture forces observed in cells. Our work suggests that nonequilibrium, physical extraction of environmental signals can make biological systems more evolvable at a moderate energy cost.