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Modeling shapes and traction forces of steady moving and perturbed cells

对稳定移动和扰动细胞的形状和牵引力进行建模

基本信息

批准号：
246963360
负责人：
Dr. Falko Ziebert
金额：
--
依托单位：
Institut für Theoretische Physik
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/246963360?language=en
关键词：
Modeling shapes traction forces steady

项目摘要

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.

真核细胞基于底物的爬行运动对许多生物学功能是必不可少的，无论是在发育过程中还是在成熟的生物体中，其功能障碍涉及多种病理过程。另一方面，活动细胞是活跃的、自推进的粒子的自然实现，这是非平衡物理学中一个非常活跃的话题。虽然对基于底物的运动性的全面理解仍然难以捉摸，但最近在整个细胞水平上的建模方面已经取得了进展。最初提案的目的是开发一个建模框架，其中包括细胞爬行的所有关键物理方面，并允许同时预测活动细胞的形状及其对基质施加的牵引力模式，这是全球力量平衡的物理痕迹。在第一个资助期，我们开发了一个考虑空间分辨牵引力的模型，允许细胞形状和动力学的广泛多样性。此外，根据目前的实验研究方向，我们改进了对膜的描述，包括了膜的张力，它作为对抗肌动蛋白聚合的全局力调节器，并将该模型推广到描述几个细胞，从而可以研究细胞的集体运动。我们现在手中有了所有的碎片，这些碎片结合在一起将使我们能够实现最初的目标。在这份第三年资助的后续提案中，我们将组装建模部件，并根据我们的外部合作者(A.Verkhovsky，洛桑)关于稳定移动和极化(即开始移动)角质细胞的实验数据进行改进和调整。此外，在推广到几个细胞的基础上，我们将研究细胞和细胞碎片的相遇，这是实验刚刚开始的地方。研究这种碰撞将进一步加强S模型的保真度，并允许在日益探索的生物相关背景下研究细胞对外部扰动的反应(参见。集体运动、拥挤)。除了单个和小型移动细胞组合的物理学之外，正在开发的模型也将对其他生物和人工驱动的软件系统有利。