An IBEC-led study has revealed how mesenchymal stem cells respond to the viscosity of their environment, a key aspect in their differentiation process. The research, published in Nature Communications, provides new insights that could revolutionise the design of biomaterials for regenerative medicine applications.
Research led by Manuel Salmeron, ICREA Research Professor at the Institute for Bioengineering of Catalonia (IBEC) and Professor of Biomedical Engineering at the University of Glasgow, has improved our understanding of how mesenchymal stem cells (MSCs) sense the viscosity of their environment, a key factor in their differentiation into different tissue types. The findings, published in Nature Communications, provide fundamental insights that could improve the design of biomaterials for regenerative medicine applications.
We usually model tissues as if they were springs. But in reality, tissues are viscoelastic, which means that when a force is applied to them, they deform and we don’t need to maintain this constant force to maintain the deformation because their internal structure reorganises itself.
Manuel Salmeron
MSCs have the ability to develop into different cell types – such as bone, cartilage or muscle cells – and their fate can depend on the physical properties of the environment in which they are found. Until now, much research has focused on the ‘stiffness’ of materials, without considering the ‘viscosity’.
‘We usually model tissues as if they were springs: we need to maintain a constant force to keep them deformed; when we release the spring, it returns to its original shape. But in reality, tissues are viscoelastic, which means that when a force is applied to them, they deform and we don’t need to maintain this constant force to maintain the deformation because their internal structure reorganises itself,’ explains Manuel Salmeron, Principal Investigator of the IBEC Microenvironments for Medicine group and last author of the study.
In order to analyse in depth how the viscous properties affect the behaviour of the cells, the team therefore ignored stiffness and worked exclusively with viscosity. Specifically, they developed an experimental model with lipid membranes that mimic the viscosity of natural tissues, allowing them to study how the interaction between adhesion proteins (integrins) and cell connecting proteins (cadherins) modulates the interaction of MSCs with their environment.
The results show that in the presence of other cells, the adhesion of MSCs to the substrate decreases, changing their behaviour and promoting their differentiation into softer tissues such as cartilage. Both the viscosity of the extracellular matrix and cell-cell interactions have a significant impact on how stem cells perceive their environment, a factor that should be taken into account when designing biomaterials.
In collaboration with the team of Pere Roca-Cusachs, professor at the University of Barcelona (UB) and Principal Investigator of the Cellular and Molecular Mechanobiology group at IBEC, the researchers adapted their previous model to include both viscosity and cell-cell interactions via cadherins. This innovative model allows them to more realistically simulate the behaviour of viscoelastic tissues in the human body.
The study is the main result of Eva Barcelona’s PhD thesis and represents a step forward in the development of materials that can guide tissue regeneration with greater precision, laying the foundations for more efficient and personalised regenerative medicine.
Referenced article:
Eva Barcelona-Estaje, Mariana A. G. Oliva, Finlay Cunniffe, Aleixandre Rodrigo-Navarro, Paul Genever, Matthew J. Dalby, Pere Roca-Cusachs, Marco Cantini & Manuel Salmeron-Sanchez. N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity. Nature Communications, 15, 8824(2024). DOI: 10.1038/s41467-024-53107-6
