论文标题
免疫细胞使用主动拉伸力来区分亲和力并加速进化
Immune cells use active tugging forces to distinguish affinity and accelerate evolution
论文作者
论文摘要
众所周知，细胞会施加力量，以感知其物理环境，以指导运动和命运决策。在这里，我们建议细胞可以从自适应免疫系统中汲取灵感来驱动自己的发展。越来越多的证据表明，免疫B细胞（能够快速达尔文进化）使用细胞骨架力从其他细胞表面积极提取抗原。为了阐明力使用的进化意义，我们开发了一种拔河抗原提取的理论，该理论将受体结合特性映射到克隆生殖适应性，揭示了选择强度的物理决定因素。该框架统一了不断发展的细胞的机械感应和亲和力歧视能力：靠近硬抗原的抗原特eters以牺牲绝对提取为代价增强了歧视严格性。因此，主动力使用可以加速适应性，但也可能导致细胞群体灭绝，从而产生最佳的拉力范围，与在细胞中观察到的分子破裂力匹配。我们的工作表明，非平衡的环境信号的物理提取可以使生物系统以中等的能源成本更具变化。
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.
