Molecular Interactions between Collagen and Fibronectin: A Reciprocal Relationship that Regulates De Novo Fibrillogenesis

A major roadblock in identifying the fundamental mechanisms underlying tissue genesis is the disparity between in vitro and in vivo observations. Differences in protein function often arise from the influence of the native molecular environment. For instance, collagen (COL) assembly proceeds spontaneously in vitro yet is strongly reliant on fibronectin (FN) in vivo. To elucidate the potential FN-COL interactions during tissue genesis, we explore their co-dependence in vitro by investigating protein binding, conformational changes, assembly kinetics, co-localization, and fiber mechanics. We find that FN accelerates COL nucleation, and in reciprocity, the presence of COL fibrils induces the formation of highly co-localized FN fibrils. Additionally, the FN-fiber-drawing process catalyzes COL incorporation at concentrations previously considered subthreshold for COL flow-induced crystallization. Our studies elucidate pathways for templating FN networks and illuminate how cells might leverage the hydrophobicity of FN and synergistic FN-COL interactions to efficiently guide production of the extracellular matrix.