GROWTH FACTOR MICROENVIRONMENTS TO HARNESS STEM CELL DIFFERENTIATION
University of Glasgow, UK
Most cells assemble rich protein matrices via an integrin-dependent mechanism that incorporates e.g. fibronectin (FN) molecules into matrix fibrils. The process involves integrin binding and activation of cell contractility to extend FN and expose cryptic domains that promote protein-protein interactions. We have shown that this process can occur by simple adsorption of individual protein molecules onto particular surface chemistries – in absence of cells. FN – material interactions would induce changes in the conformation of individual FN molecules to expose of self-assembly sites and drive FN assembly into nanonetworks at the material interface, a process that we have named material-driven fibronectin fibrillogenesis. This FN matrix assembled at the material interface involves conformational changes of FN upon adsorption that allows simultaneous availability of the integrin binding (FNIII9-10) and growth factor binding (FNIII12-14) regions.
The resulting material-driven FN matrix assembled at the material interface consists of a protein network with enhanced biological activity: it supports cell adhesion, matrix remodelling, and trigger cell differentiation. Moreover, it provides a robust platform to engineer advanced microenvironments in combination with growth factors to tune stem cell differentiation and promote tissue repair. Here we show the potential of the system to regenerate bone using BMP-2 as well as the ability to promote vascularisation by incorporating VEGF into the system.