Mechanical regulation of cell division: Speed versus Strength

Cells within biological tissues must respond to internal and external mechanical forces to maintain tissue structure, ensure tissue homeostasis and coordinate embryonic development. Mechanical regulation of cell division is emerging as a key route to control proliferation in tissues, but our knowledge of the mechanisms involved is still in its infancy. This is important considering the mechanical strains experienced in proliferating tissues during embryonic development and in common diseases, such as cancer. A major gap in our understanding is how the speed of mechanical change impacts mechano- regulation. Most studies expose cells to fast, instantaneous, changes in mechanical strain but in vivo tissues frequently experience a much slower build-up of strain, such as during morphogenesis or fibrosis. Crucially, in preliminary work, we find a marked difference in division response when tissue is stretched at different speeds. We will use a combination of tissue-stretch and tailored mathematical and computational modelling to determine how the speed versus strength of strain regulates cell division in complex tissue environments. Unravelling how tissues respond to strain rate provides a new window into the fundamentals of mechano-regulation not previously explored and will reveal mechanisms vital to tissue function that can be exploited in regenerative medicine.