Contractile forces during cancer cell migration in a 3-D connective tissue matrix

拟议项目的总体目标是描述癌细胞在通过三维结缔组织基质迁移过程中产生的机械力。我们提出了两个具体目标。第一个目标是开发一种方法，用于测量单个细胞在结缔组织基质迁移过程中对周围环境施加的牵引力。第二个目标是验证这样一个假设，即癌细胞在结缔组织基质中的迁移是通过产生更高的力量来增强的。我们将分析作用力的产生与肿瘤细胞侵袭的关系，作为基质硬度、基质蛋白浓度、基质支架的网目大小和细胞周围蛋白分解的函数。这些数据将帮助我们理解力量生成在肿瘤侵袭中的作用，并可能有助于解释肿瘤在转移形成过程中关于侵袭力和组织偏好的特异性差异。

The general aim of the proposed project is to characterize the mechanical forces that cancer cells generate during their migration through a 3-dimensional connective tissue matrix. We propose two specific aims. The first aim is to develop a method for measuring the tractions that single cells exert on their surroundings during migration in a connective tissue matrix. The second aim is to test the hypothesis that cancer cell migration in a connective tissue matrix is augmented by the ability to generate higher forces. We will analyze the relationship between force generation and tumor cell invasion as a function of matrix stiffness, matrix protein concentration, mesh-size of the matrix scaffold, and pericellular proteolysis. These data will help us to understand the role of force generation for tumor invasion, and may help explain tumor-specific differences regarding invasiveness and tissue preferences during metastasis formation.