Department of Physics and Astronomy, University of California Los Angeles, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2213067120. doi: 10.1073/pnas.2213067120. Epub 2023 Mar 10.
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.
细胞被认为会产生力来感知周围的物理环境，从而指导运动和命运决策。在这里，我们提出，细胞可能会像适应性免疫系统那样，通过机械功来推动自身进化。越来越多的证据表明，能够快速进行达尔文式进化的免疫 B 细胞利用细胞骨架力从其他细胞表面主动提取抗原。为了阐明力的使用的进化意义，我们开发了一种拔河式抗原提取理论，该理论将受体结合特征映射到克隆生殖适应性上，揭示了选择强度的物理决定因素。该框架统一了进化细胞的机械感应和亲和力识别能力：抵抗刚性抗原系绳的拉力增强了区分的严格性，而牺牲了绝对提取的效率。因此，主动用力可以加速适应，但也可能导致细胞群体灭绝，从而产生与细胞中观察到的分子断裂力相匹配的最佳拉力范围。我们的工作表明，非平衡、物理提取环境信号可以使生物系统以适度的能量成本更具进化能力。
