Quantitative Models of Cell Shape and Motion

细胞形状和运动的定量模型

• 批准号: 6829172
• 负责人: MICAH DEMBO
• 金额: $ 26.15万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6829172
• 关键词: 3T3 cells; biomechanics; cell adhesion; cell migration; cell morphology; cell motility; computer simulation; fibroblasts; model design /development; protoplasm motility

DESCRIPTION (provided by applicant): Control of cell shape and motion is a key aspect of development, wound healing, tissue remodeling, immune response, and unfortunately, tumor invasion and metastasis. Thus, a better understanding of the mechanics of cells will have implications not only for ideas about cellular function, but also for approaches to the many problems of cellular dysfunction (e.g. cancer, maladaptive remodeling in heart failure, etc.) that are responsible for much of the medical burden borne by an aging US population. From a mechanical viewpoint, amoeboid cells are flexible, membrane-enclosed bags filled with cytoskeletal polymers and molecular motors. Collectively, these agents maintain cell shape, orchestrate cell movements, and produce active forces as required by circumstances. When cultured on flat surfaces, most cells spread to take on a pancake shape. Motion is then mediated by a thin lamellipodium at the leading edge via a cycle of protrusion, adhesion and traction that pulls forward posterior regions of the cell. It is the overall goal of this application to develop a better understanding of the dynamics underlying these events by constructing and testing quantitative models of cellular morphology, motion, and force production. The specific aims are: 1. To contruct two-dimensional computer models (i.e. transverse sections in length and height) of lamellae and of whole fibroblasts with a view toward exploring not only lamellipodial protrusion, but also such phenomena as blebbing, ruffling and surface waves. 2. To develop a continuum mechanics theory of free-boundary flows in the "shallow-water' approximation appropriate for the study of thin layers such as lamellae. This will be the foundation for a "two and a half"-dimensional computer code (x,y and height parameter) able to model cytoplasmic flows in spread cells. 3. To use this shallow-water computational tool to model whole cell migration on a surface. Emphasis will be put on the analysis of popular experimental systems of motility such as fish keratocytes or 3T3 fibroblasts.

描述（由申请人提供）：细胞形状和运动的控制是发育、伤口愈合、组织重塑、免疫反应以及肿瘤侵袭和转移的关键方面。因此，更好地理解细胞的机制不仅会对细胞功能的想法产生影响，而且还会对许多细胞功能障碍问题（例如癌症，心力衰竭中的不适应重塑等）的方法产生影响，这些问题是造成美国人口老龄化医疗负担的主要原因。从机械角度来看，变形虫细胞是柔性的、膜封闭的袋子，里面充满了细胞骨架聚合物和分子马达。总的来说，这些因子维持细胞形状，协调细胞运动，并根据环境需要产生积极的力量。当在平面上培养时，大多数细胞扩散成煎饼状。运动由前缘的薄板基通过一个突出、粘附和牵引的循环来调节，该循环将细胞的后部向前拉。该应用程序的总体目标是通过构建和测试细胞形态、运动和力产生的定量模型，更好地理解这些事件背后的动力学。具体目标是：