Relatore: Chris Lorenz (Biophysics & Soft Matter Research Group, Department of Physics, King’s College London, UK)

Abstract: 

Fibronectin (FN) is a large extracellular matrix glycoprotein that affects many cell processes including differentiation, migration and proliferation. FN’s function requires its quaternary structure to transition from a compact to an extended form, a process that is integrin dependant and leads to FN network formation. Recently, Prof. Manuel Salmeron-Sanchez’s group in Glasgow has carried out a significant amount of research on an alternative to this integrin dependant process - a material driven approach, with the majority of the work carried out on poly (methyl/ethyl) acrylates. FN on poly(ethyl acrylate) assumes the extended form, leading to network assembly, whereas the chemically similar surface poly(methyl acrylate) shows FN aggregation and no network formation. To gain further insight into how such a small difference in the surface chemistry has such drastic consequences in FN’s structure, we used molecular dynamics to simulate the crucial domains FN III 9-10 on self-assembled monolayers (SAMs) that were functionalised using the previously mentioned polymer’s side chains. Additionally, we have investigated the adsorption of the same domains of FN to a methyl-terminated SAMs, which has also been observed to lead to fibrillogenesis experimentally.  Finally, more recently, we have also investigated the interaction of the same FN III 9-10 domains with DOPC and DPPC, as there has been recent experimental evidence that fibronectin preferably binds to DPPC domains in mixed DOPC/DPPC bilayers.  In doing so, we have identified the role of interfacial water in the different binding behaviours observed to these various interfaces, as well as the specific residues which interact with the interfaces.