权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Quantitative Models of Cell Shape and Motion

细胞形状和运动的定量模型

基本信息

批准号：
7240548
负责人：
MICAH DEMBO
金额：
$ 22.78万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-06-01 至 2010-05-31
项目状态：
已结题

项目摘要

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、免疫应答以及不幸的是肿瘤侵袭和转移的关键方面。因此，更好地理解细胞的力学不仅对细胞功能的想法有影响，而且对细胞功能障碍的许多问题（例如癌症，心力衰竭中的适应不良重塑等）的方法也有影响。这些疾病是美国老龄化人口医疗负担的主要原因。从力学的角度来看，变形虫细胞是充满细胞骨架聚合物和分子马达的柔性膜封闭袋。总的来说，这些代理人保持细胞形状，协调细胞运动，并根据情况需要产生积极的力量。当在平坦表面上培养时，大多数细胞扩散成煎饼形状。然后，运动由前缘的薄板状伪足介导，通过突出、粘附和牵引的循环，向前拉动细胞的后部区域。本申请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来更好地理解这些事件背后的动力学。具体目标是： 1.目的：建立板层和整个成纤维细胞的二维计算机模型（即长度和高度的横切面），以探讨板层脂肪突，以及气泡、皱褶和表面波等现象。 2.在“浅水”近似下发展一种自由边界流动的连续介质力学理论，适用于研究薄层，如层流。这将是一个“两个半”维的计算机代码（x，y和高度参数），能够模拟细胞质流动的基础。 3.使用这种浅水计算工具来模拟整个细胞在表面上的迁移。重点将放在流行的实验系统的运动，如鱼类角膜细胞或3T3成纤维细胞的分析。