Modeling shapes and traction forces of steady moving and perturbed cells

真核细胞的基于基质的爬行运动对于许多生物学功能是必不可少的，无论是在发育期间还是在成熟的生物体中，并且其功能障碍涉及几种病理学。另一方面，运动细胞是一种自然实现的积极的，自我推进的粒子，一个非常活跃的主题，在非平衡物理。虽然对基于底物的运动性的全面理解仍然难以捉摸，但最近在全细胞水平上的建模方面取得了进展。原始提案的目的是开发一个建模框架，该框架包括细胞爬行的所有关键物理方面，并且允许同时预测运动细胞的形状和它们施加在基底上的牵引力模式，作为全局力平衡的物理痕迹。在第一个资助期间，我们开发了一个模型，该模型考虑了空间分辨的牵引力，允许细胞形状和动力学的广泛多样性。此外，针对当前的实验研究方向，我们改进了膜的描述，包括它的张力，它作为一个全球性的力调节器抵消肌动蛋白聚合，并概括了模型来描述几个细胞，允许研究集体细胞运动。我们现在已经掌握了所有的要素，这些要素结合在一起将使我们能够实现最初的目标。在第三年资助的后续提案中，我们将组装模型部件，并根据外部合作者的实验数据对其进行改进和调整（A。Verkhovsky，洛桑）对稳定移动和极化（即开始移动）的角膜细胞的研究。此外，基于对几个细胞的推广，我们将研究细胞和细胞碎片的相遇，其中实验刚刚开始。研究这种碰撞将进一步加强模型的保真度，并允许在生物学相关的背景下研究细胞对外部扰动的反应，这种背景越来越多地被探索（参见。集体运动，拥挤）。除了移动细胞的单个和小集合体的物理学之外，正在开发的模型也将对其他生物和人工驱动的软系统有益。

The substrate-based crawling motion of eukaryotic cells is essential for many biological functions, both during development and in the mature organism, and its dysfunction is involved in several pathologies. On the other hand, motile cells are a natural realization of active, self-propelled particles, a very active topic in nonequilibrium physics. Although a comprehensive understanding of substrate-based motility remains elusive, progress has been achieved recently in its modeling on the level of a whole cell. The aim of the original proposal was to develop a modeling framework that includes all key physical aspects of cell crawling and that would allow a simultaneous prediction of the shapes of motile cells and the traction force patterns they exert on the substrate, being the physical traces of the global force balance. During the first funding period we developed a model accounting for spatially resolved traction forces, allowing for a wide diversity of cell shapes and dynamics. In addition, reacting to current experimental research directions, we improved the description of the membrane by including its tension, which acts as a global force regulator counteracting actin polymerization, and generalized the model to describe several cells, allowing to study collective cellular motion. We now have all the pieces in hand that combined will allow us to achieve the original goal. In this follow-up proposal for a third year of funding we will assemble the modeling parts and refine and adjust them to the experimental data from our external collaborator (A. Verkhovsky, Lausanne) on steady moving and polarizing (i.e. starting to move) keratocyte cells. In addition, based on the generalization to several cells, we will study encounters of cells and cell fragments, where experiments have just been started. Investigating such collisions will further strengthen the model s fidelity, and allow to study the cellular response to external perturbations in a biologically relevant context that becomes increasingly explored (cf. collective motion, crowding). Apart from the physics of single and small ensembles of moving cells, the model under development will also be of profit for other, biological and artificial, driven soft systems.