Interplay between viscoelasticity and stiffness as essential properties in mechanobiology

Over the last ten years, there has been a significant surge in mechanobiological research aimed at elucidating how substrate stiffness alters cell biology and the stiffness of multicellular systems. Although the concept of ‘stiffness,’ is employed to describe the material characteristics of both cells and their substrates, it lacks a precise definition within the realms of soft matter physics and rheology. Generally, stiffness can be understood as the degree to which a material resists deformation when subjected to a mechanical force. It is well established that both multicellular systems and substrate matrices exhibit viscoelastic behaviour. The stiffness of these viscoelastic systems is not constant; rather, it is influenced by the interplay between energy storage, which tends to increase stiffness, and energy dissipation, which tends to reduce it. These processes can occur simultaneously or at different rates. The traction forces exerted by cells can induce alterations in the substrate matrix, thereby modifying its stiffness, which in turn affects the efficiency of cell migration and the overall stiffness of a multicellular system. The mechanisms through which cells detect variations in the viscoelastic properties of their surroundings are still being explored, and they are influencedby the rates and magnitudes of energy storage and dissipation. This discussion of stiffness is contextualized through the examination of collective migration in epithelial and mesenchymal monolayers on collagen I matrices, drawing on both experimental findings and rheological constitutive models.