Conformational changes of exogenous deposited fibronectin on decellularized aortic conduits after implantation

Abstract

Plasma fibronectin (FN) is produced by hepatocytes and released into circulation as a soluble compact dimer at concentrations of 200-600 μg/ml. Circulating plasma FN is a glycoprotein dimer and multidomain protein with high molecular weight (440-500 kDa) that is folded into a globular compact structure. Its compact structure leads to the inactivation of FN since major functional binding sites are buried.Fibronectin, a pervasive extracellular matrix component, plays a vital role in modulating diverse cellular functions through direct interactions with integrin receptors on cell surfaces. Our previous research demonstrated that fibronectin facilitates the autologous cellular repopulation of implanted decellularized grafts, enhancing adhesion capacity and biocompatibility via fibronectin fibrillogenesis. Interestingly, the supportive effect varied across different regions of the implanted decellularized grafts. This prompted an inquiry into whether there are conformational differences in fibronectin deposited on the luminal and adventitial surfaces of decellularized aortic conduits post-implantation. In this study, we employed a doubly labeled fibronectin with a fluorescent resonance energy transfer (FRET) pair, utilizing it to analyze variations in conformational changes of adsorbed fibronectin at distinct sites within the decellularized aortic conduits. This investigation sheds light on the nuanced interactions between fibronectin and decellularized grafts, offering valuable insights into the intricacies of cellular repopulation dynamics in different regions of implanted conduits.