James Franck Institute, University of Chicago, Chicago, IL 60637, USA; Department of Physics, University of Chicago, Chicago, IL 60637, USA; Kadanoff Center for Theoretical Physics, University of Chicago, Chicago, IL 60637, USA.
Department of Cell & Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
Cell. 2024 Jan 18;187(2):481-494.e24. doi: 10.1016/j.cell.2023.11.041. Epub 2024 Jan 8.
Cellular form and function emerge from complex mechanochemical systems within the cytoplasm. Currently, no systematic strategy exists to infer large-scale physical properties of a cell from its molecular components. This is an obstacle to understanding processes such as cell adhesion and migration. Here, we develop a data-driven modeling pipeline to learn the mechanical behavior of adherent cells. We first train neural networks to predict cellular forces from images of cytoskeletal proteins. Strikingly, experimental images of a single focal adhesion (FA) protein, such as zyxin, are sufficient to predict forces and can generalize to unseen biological regimes. Using this observation, we develop two approaches-one constrained by physics and the other agnostic-to construct data-driven continuum models of cellular forces. Both reveal how cellular forces are encoded by two distinct length scales. Beyond adherent cell mechanics, our work serves as a case study for integrating neural networks into predictive models for cell biology.
细胞的形态和功能源自细胞质中复杂的机械化学系统。目前,还没有系统的策略可以根据细胞的分子成分来推断其大规模的物理性质。这是理解细胞黏附和迁移等过程的障碍。在这里,我们开发了一种数据驱动的建模管道来学习贴壁细胞的力学行为。我们首先训练神经网络从细胞骨架蛋白的图像中预测细胞力。令人惊讶的是,单个粘着斑(FA)蛋白(如黏着斑蛋白)的实验图像足以预测力,并且可以推广到未知的生物学状态。利用这一观察结果,我们开发了两种方法——一种受物理约束,另一种不受约束——来构建细胞力的基于数据的连续体模型。这两种方法都揭示了细胞力是如何由两个不同的长度尺度编码的。除了贴壁细胞力学之外,我们的工作还为将神经网络集成到细胞生物学的预测模型中提供了一个案例研究。