Mesenchymal Stem Cells Sense the Toughness of Nanomaterials and Interfaces.

Stem cells are known to sense and respond to a broad range of physical stimuli arising from their extra-cellular environment. In particular, the role of the mechanical properties (Youngs or shear modulus, viscoelasticity) of biomaterials has extensively been shown to have a significant impact on the adhesion, spreading, expansion and differentiation of stem cells. 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, we show 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 assembly of poly(L-lysine) nanosheets at liquid-liquid interfaces is characterised via interfacial shear rheology. The interfacial viscoelasticity and toughness of resulting nanosheets are then characterised, together with the imaging of corresponding interfaces via epifluorescence microscopy. 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 MSCs to adhesion and culture at corresponding interfaces is investigated via immunostaining and confocal microscopy. This article is protected by copyright. All rights reserved.