Mesenchymal Stem Cells Sense the Toughness of Nanomaterials and Interfaces

Stem cells are known to sense and respond to the mechanical properties of biomaterials. In turn, cells exert forces on their environment that can lead to striking changes in shape, size and contraction of associated tissues, and may result in mechanical disruption and functional failure. However, no study has so far correlated stem cell phenotype and biomaterials toughness. Indeed, disentangling toughness-mediated cell response from other mechanosensing processes has remained elusive as it is particularly challenging to uncouple Youngs' or shear moduli from toughness, within a range relevant to cell-generated forces. In this report, it is shown how the design of the macromolecular architecture of polymer nanosheets regulates interfacial toughness, independently of interfacial shear storage modulus, and how this controls the expansion of mesenchymal stem cells at liquid interfaces. The viscoelasticity and toughness of poly(l-lysine) nanosheets assembled at liquid-liquid interfaces is characterised via interfacial shear rheology. The local (microscale) mechanics of nanosheets are characterised via magnetic tweezer-assisted interfacial microrheology and the thickness of these assemblies is determined from in situ ellipsometry. Finally, the response of mesenchymal stem cells to adhesion and culture at corresponding interfaces is investigated via immunostaining and confocal microscopy.

Automated summary

Stem cells can sense and respond to the mechanical properties of biomaterials, and their forces exerted on the environment can lead to changes in tissue shape, size, and contraction, potentially causing mechanical disruption and functional failure. This study focuses on the correlation between stem cell phenotype and biomaterials toughness, which has been elusive due to the challenge of uncoupling Youngs' or shear moduli from toughness. The design of polymer nanosheets' macromolecular architecture is found to regulate interfacial toughness, and this control affects the expansion of mesenchymal stem cells at liquid interfaces.