Significance
The ability of cells to sense and respond to mechanical forces underlies many important processes in biology, from morphogenesis to cancer metastasis. However, whether and how active force usage would influence cells’ capacity to evolve remains unknown. Here, we investigate immune response as a key example to demonstrate that cells can do physical work to modulate their own evolution. By mapping receptor traits to clonal fitness via nonequilibrium antigen extraction, we introduce a mathematical framework that recapitulates mechanosensing and discrimination capabilities of immune cells, allows to infer intrinsic energy landscapes from data, and rationalizes the utility of active molecular processes for efficient organismic adaptation. We propose that tactile sense of cells can strongly shape their evolution.
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 antigens from other cells’ surfaces. 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.
