Alonso Albert, Kirkegaard Julius B, Endres Robert G
Niels Bohr Institute, University of Copenhagen, Copenhagen 2100, Denmark.
Department of Computer Science, University of Copenhagen, Copenhagen 2100, Denmark.
Proc Natl Acad Sci U S A. 2025 May 13;122(19):e2502368122. doi: 10.1073/pnas.2502368122. Epub 2025 May 8.
Single-cell organisms and various cell types use a range of motility modes when following a chemical gradient, but it is unclear which mode is best suited for different gradients. Here, we model directional decision-making in chemotactic amoeboid cells as a stimulus-dependent actin recruitment contest. Pseudopods extending from the cell body compete for a finite actin pool to push the cell in their direction until one pseudopod wins and determines the direction of movement. Our minimal model provides a quantitative understanding of the strategies cells use to reach the physical limit of accurate chemotaxis, aligning with data without explicit gradient sensing or cellular memory for persistence. To generalize our model, we employ reinforcement learning optimization to study the effect of pseudopod suppression, a simple but effective cellular algorithm by which cells can suppress possible directions of movement. Different pseudopod-based chemotaxis strategies emerge naturally depending on the environment and its dynamics. For instance, in static gradients, cells can react faster at the cost of pseudopod accuracy, which is particularly useful in noisy, shallow gradients where it paradoxically increases chemotactic accuracy. In contrast, in dynamics gradients, cells form de novo pseudopods. Overall, our work demonstrates mechanical intelligence for high chemotaxis performance with minimal cellular regulation.
单细胞生物和各种细胞类型在遵循化学梯度时会采用一系列运动模式,但尚不清楚哪种模式最适合不同的梯度。在这里,我们将趋化性变形虫细胞中的定向决策建模为一种依赖刺激的肌动蛋白招募竞赛。从细胞体伸出的伪足竞争有限的肌动蛋白池,以将细胞推向它们的方向,直到一个伪足获胜并确定运动方向。我们的最小模型提供了对细胞用于达到精确趋化性物理极限的策略的定量理解,与没有明确梯度传感或持续存在的细胞记忆的数据一致。为了推广我们的模型,我们采用强化学习优化来研究伪足抑制的效果,伪足抑制是一种简单但有效的细胞算法,通过该算法细胞可以抑制可能的运动方向。根据环境及其动态变化,基于不同伪足的趋化策略自然出现。例如,在静态梯度中,细胞可以以伪足准确性为代价更快地做出反应,这在嘈杂、浅梯度中特别有用,在这种情况下,它反而会提高趋化准确性。相比之下,在动态梯度中,细胞会形成新的伪足。总体而言,我们的工作展示了在最少细胞调节下实现高趋化性能的机械智能。