Abstract

Engineered synergistic growth factor microenvironments

Manuel Salmeron-Sanchez, Professor of Biomedical Engineering, University Of Glasgow

Growth factors are ubiquitous molecules in tissue development and homeostasis, and are key components in regenerative medicine strategies. In vivo, growth factors are bound to the extracellular matrix, a fibrillar mesh of proteins that provides mechanical support and cell function, including adhesion, migration and differentiation. Most cells assemble rich protein matrices via an integrin-dependent mechanism that incorporates protein molecules (e.g. fibronectin, FN) 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. Protein – material interactions would induce changes in protein conformation to expose of self-assembly sites and drive protein assembly into nanonetworks at the material interface, a process that we have named material-driven fibrillogenesis. The resulting material-driven 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 on a chip in combination with growth factors, to tune stem cell differentiation and enhance vascularisation.