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

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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.