The (extracellular) matrix is viscous and it matters

Stem cells underpin regenerative medicine, as they have the potential to differentiate into different lineages, giving rise to e.g. bone or cartilage or even neural cells. Yet the mechanisms to control stem cell differentiation are mostly limited to complex biochemical cocktails of growth factors and cytokines. Almost 20 years ago, it was reported that the elastic properties of the extracellular matrix can also control stem cell differentiation - the community was then immersed in understanding that mechanical aspect of stem cells that impact their behaviour, including not only stem cell differentiation but also embryonic development and cancer. However, we know that tissues, the extracellular matrix, are viscoelastic solids and then their viscosity in addition to their elasticity must be considered to understand the mechanical aspect of cells.Here, we demonstrated that the strength of adhesion of stem cells increases with the viscosity of the extracellular matrix. This is important as there is a direct correlation between this cell adhesion strength and the phenotype that stem cells differentiate into. For example, if the adhesion strength is high, stem cells differentiate into osteoblasts and they acquire softer phenotypes (such as adipocytes) if this strength of adhesion decreases. Viscosity offers then a mechanical way to control stem cell phenotypes and control their differentiation. Yet, stem cells also interreact with other neighbouring cells and strikingly our work demonstrates that this interaction with other cells soften their strength of adhesion to the extracellular matrix. This means that the way stem cells feel viscosity depends on whether they are by themselves or as part of a community of cells! The work shows how fundamental understanding of cell mechanobiology is key to the design of biomaterials – which are basically synthetic extracellular matrices – with controlled mechanical properties to be used in regenerative medicine.