IPLS/BioP Webinar: Dr. Alberto Elosegui Artola (Francis Crick Institute)

Abstract: The mechanical properties of the extracellular matrix (ECM) regulate cellular processes during development, cancer and wound healing. The vast majority of research efforts in this field have focused on the ECM’s elasticity as a leading determinant of cell and tissue behaviour. We have previously shown the biophysical mechanism which cells sense tissue elasticity and transduce it into downstream signaling and how force transmitted from the ECM to the nucleus is enough to translocate transcriptional regulators to the nucleus. However, the ECM is not merely elastic but is instead both viscous and elastic. Despite the universality of ECM’s viscoelasticity, how viscoelasticity affects tissue function is unknown. I will present our results where we show that the passive viscoelastic properties of the ECM can regulate multicellular tissues spatial and temporal organization both in breast spheroids and intestinal organoids. By combining computational modelling with experiments, we confirm that the viscoelastic properties of the matrix regulate spherical tissues symmetry breaking, invasion and branching. Furthermore, ECM viscoelasticity controls epithelial to mesenchymal transition and tumour growth both in vitro and in vivo. Altogether, our work demonstrates the role of viscoelasticity in symmetry breaking instabilities associated with fingering, a fundamental process in morphogenesis and oncogenesis, and suggest ways of controlling tissue form using the extracellular matrix. 

Host: Thomas Michaels

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