Biomechanics of collective chemotaxis (360G-Wellcome-102489_Z_13_Z)

Collective chemotaxis (CCT), whereby groups of cells collectively migrate in response to chemotactic signals, is a fundamental mode of migration in development and metastatic cancers. The biomechanics of this process has been largely overlooked, with most work focusing on spontaneous migration of epithelial sheets despite evidence that strong cell-cell adhesions are not required for collective migration. Additionally, chemotactic signals are important for directional migration in vivo. We propose to use neural crest (NC) cells, a highly invasive mesenchymal cell population that extensively migrate throughout the embryo, to address the biomechanics of CCT. We will perform high-resolution time-lapse imaging of Xenopus NC to assess physical properties of CCT such as velocity and viscosity. Traction force microscopy, FRET tension sensors and atomic force microscopy shall be used to measure the physical forces required for CCT. Finally, the molecular mechanisms necessary for the biomechanics of this process shall be identified, in particular through chemical and mechanical manipulation of the actomyosin cytoskeleton tounderstand how it contributes to providing forces for CCT. Collectively, theseresults will provide a novel insight into the biomechanics of CCT which could have important implications for morphogenetic processes, regeneration and diseases like invasive tumours.