Effects of a biophysically defined environment on cells of different developmental origin: a contribution for the development of versatile biomaterials

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Similar to biochemical factors, biophysical cues govern multiple cell functions. In this regard, in medicine and dentistry, cell-carrying biomaterials, which control therapy-relevant cell functions through their material-inherent biophysical properties, are still not available. In this context, the fundamental question has not yet been answered, whether a defined biophysical cue has similar effects on cell morphology and phenotype, even in cells of different developmental origin, and, if true, if this effect is possibly processed by the same signaling molecules. In this case, the same defined biophysical cue could be used to control cells of different developmental origin. Within the project, mesenchymal stromal (MSCs) of the mesoderm and ectodermal epithelial gingival keratinocytes will be cultivated on nanofiber scaffolds. These commercially available scaffolds will be defined and characterized by the applicants in regard to the innate scaffold (i) fiber thickness and (ii) fiber densities and the resulting substrate stiffness. The effects of these biophysically defined extracellular cues on cell morphology, proliferation and differentiation as well as the herewith connected activation of signaling molecules will be analyzed in both cell entities, also including mechanistic approaches. We will focus on signaling molecules, emerging from focal adhesions (FAs) and the cell-to-cell contact-mediating cadherin system, both of which are essentially involved in the intracellular processing of biophysical cues. The analyses will be based on established, standardized methods to quantify cell morphology, gene and protein expression of biofunctional markers, activation/phosphorylation of signaling molecules, and statistical comparisons. Mechanistic analyses will be conducted by using specific inhibitors and RNAi. Characterization of material properties includes scanning electron microscopy and nanoindentation. Taken together, the resulting data will facilitate answering the central question of the proposal, if the same biophysical cues activate the same signaling molecules in cells of different developmental origin, and herein mediate comparable effects. The knowledge gained can be implemented in the development of biophysically-tailored biomaterials to control therapy-relevant cell functions for therapeutically utilized cells.