Mathematical modeling and Computational Analysis of Cell Tissue Movement

细胞运动在多细胞生物体的胚胎发育、血管生成、组织再生、免疫应答和伤口愈合过程中起着重要作用。 在这个项目中要解决的主要问题是（i）运动的形状变化，（ii）建模的细胞内力学，和（iii）整合信号，肌动蛋白动力学和力学在一个综合的计算模型的细胞运动。 在此之前，数学建模主要集中在间充质模式上，但研究人员首先解决了连续体的另一端。 我们的总体目标是产生一个统一的描述运动在三维细胞外基质，集成信号和力学。 通过形状变化的运动尚未在所提出的上下文中进行研究，但最近已被证明在许多细胞类型的运动中是重要的，并且理解影响这种运动的速度和效率的因素是一个具有挑战性的问题。 该项目开发了数学模型，可用于研究和量化各种因素的重要性，例如影响运动效率的周围介质的属性。 第三个部分继续以前的工作，由主要研究者对信号，并将整合控制网络的模型与机械组件，包括第一个主题。 这将导致第一个模型，结合信号和力学，并将导致一个计算工具，应该是非常有用的更广泛的社区。细胞运动是一个非常复杂的过程，涉及空间和时间的控制和整合的一些子过程，包括从环境中的化学或机械信号的转导，细胞内的生化反应，以及将细胞内和细胞外信号转化为机械响应。 虽然许多单细胞生物使用鞭毛或纤毛游泳，但缺乏这种结构的真核细胞使用两种基本的运动模式-间充质和变形虫。 前者，其特点是什么？爬行？在成纤维细胞中还是滑翔？在角膜细胞中，涉及指状伪足和/或宽平板状伪足的延伸，其突起由前缘处的肌动蛋白聚合驱动。在变形虫模式中，细胞不依赖于强粘附，更圆，并利用形状变化来移动-实际上是“在人群中推挤”或“游泳”。 然而，最近的实验表明，许多细胞类型在运动中表现出巨大的可塑性，因为它们可以感知环境的机械特性并调整模式之间的平衡。因此，纯爬行和纯游泳是连续运动策略的极端，但许多细胞可以感知它们的环境，并在给定的环境中使用最有效的策略。 该项目使用创新的数学方法来更好地理解细胞运动的动力学，将新模型与实验数据相结合。 此外，研究团队包括博士后研究人员和研究生，该项目提供了在固有的跨学科领域工作的机会。

Cell locomotion plays an essential role during embryonic development, angiogenesis, tissue regeneration, the immune response, and wound healing in multicellular organisms. The major problems to be addressed in this project are (i) movement by shape changes, (ii) modeling of the intracellular mechanics, and (iii) integration of signaling, actin dynamics and mechanics in an integrated computational model of cell movement. Heretofore mathematical modeling has primarily focused on the mesenchymal mode, but the investigators first address the other end of the continuum. The overall objective is to produce a unified description for locomotion in a three-dimensional extracellular matrix that integrates signaling and mechanics. Movement by shape changes has not been studied in the context proposed, but it has recently been shown to be important in the movement of a number of cell types, and understanding the factors that affect the speed and efficiency of such movement is a challenging problem. This project develops mathematical models that can be used to study and quantify the importance of various factors, such as properties of the surrounding medium, that affect the efficiency of movement. The third component continues previous work by the principal investigator on signaling and will integrate a model of the control networks with the mechanical components that comprise the first topics. This will lead to the first model that incorporates both signaling and mechanics, and will result in a computational tool that should be very useful to the broader community.Cell movement is a very complex process that involves the spatial and temporal control and integration of a number of subprocesses, including the transduction of chemical or mechanical signals from the environment, intracellular biochemical responses, and translation of the intra- and extracellular signals into a mechanical response. While many single-celled organisms use flagella or cilia to swim, there are two basic modes of movement used by eukaryotic cells that lack such structures--mesenchymal and amoeboid. The former, which can be characterized as ?crawling? in fibroblasts or ?gliding? in keratocytes, involves the extension of finger-like pseudopodia and/or broad flat lamellipodia, whose protrusion is driven by actin polymerization at the leading edge. In the amoeboid mode, which does not rely on strong adhesion, cells are more rounded and employ shape changes to move--in effect 'jostling through the crowd' or 'swimming'. However, recent experiments have shown that numerous cell types display enormous plasticity in locomotion, in that they sense the mechanical properties of their environment and adjust the balance between the modes. Thus pure crawling and pure swimming are the extremes on a continuum of locomotion strategies, but many cells can sense their environment and use the most efficient strategy in a given context. This project uses innovative mathematical approaches to better understand the dynamics of cell locomotion, combining novel models with experimental data. Additionally, the research team includes postdoctoral researchers and graduate students, with the project providing an opportunity to work in an inherently interdisciplinary field.