Fundamental biological processes including morphogenesis, tissue repair, and tumour metastasis require collective cell motions, and to drive these motions cells exert traction forces on their surroundings. The mechanisms underlying this basic principle of health and disease have been debated intensively and, using a variety of methods in vivo, in vitro, and in silico, much conflicting evidence has accumulated. This conflicting evidence has been in every case indirect or inferential, however, because within the moving cell group the physical forces themselves have remained inaccessible to direct experimental observation. To fill this gap, this ERC application describes an interdisciplinary project to uncover the physical mechanisms underlying collective cell migration. In Objective 1, I propose to develop technology to map forces that cells within moving groups exert on each other and on their extracellular matrix. In Objective 2, we will use siRNA technology to provide a systematic analysis of the genes that regulate force generation and transmission in a migrating epithelial cell sheet. In Objective 3, we will use this pool of data to establish a constitutive link between genes, forces and collective cell motion. Although these Objectives present major technical and scientific challenges, the feasibility of each is supported by a unique technical know-how and by a productive track record in the field of cell biophysics.