The directional and synchronised movement of large groups of cells or cell clusters - also known as directed collective cell migration (dCCM) - is key during our embryonic development and when our wounds heal, but also in unfortunate scenarios such as when tumour cells undergo metastasis. Cell clusters migrate across complex environments composed of biochemical and biophysical cues. Despite this, the field has mostly focused on studying chemical guidance (chemotaxis) of dCCM - and the role of biophysical cues such as mechanical or electrical stimuli remains comparatively less understood. In this context, the mechanisms that guide dCCM in living tissues (in vivo) remain unclear. Thus, our overall goal is to complement the classic chemocentric view by addressing whether and how biophysical cues contribute to dCCM in vivo. To tackle this challenging aim, we study durotaxis (mechanical guidance) and electrotaxis (electrical guidance) at two levels: i) Tissue level, where we map mechanical and electrical properties in vivo and we test their relative contribution to dCCM; ii) Cellular level, here we explore the mechanisms by which cells sense, respond and integrate these biophysical cues. To address this, we take advantage of the innovative toolbox we developed to study mechanical and electrical cues in living tissues. As dCCM occurs in different biological contexts, we aim to generalise our results by studying dCCM of Xenopus neural crest cells, an embryonic cell population (WP1, WP2; Figure 01a); and the migration of the recently discovered Regeneration Organizing Cells (ROCs) during animal regeneration (WP3; Figure 01b). Demonstrating durotaxis and electrotaxis in vivo has proven to be a challenging goal. Thus, we expect our research to be a breakthrough across fields, bringing new perspectives and tools to study the biophysics of dCCM in vivo. This action is opening new research avenues for my lab and for others in the field, in which the interplay of biophysical and biochemical cues from the environment could be studied, paving the way to the formulation of a new and more integrative view of dCCM. Finally, revealing this information is important as we can shed lights on the mechanisms underlying embryonic defects, improve wound healing therapies and eventually understand more about how cancer cells move. In the long term this information can contribute to the design of predictive medical approaches and therapies.
