Abstract
In recent years there has been significant interest in the development of material surfaces that can control their interactions with proteins for mediating subsequent cell attachment. Such biointerfaces can have applications in e.g. medical devices and biosensors. However, non-specific adsorption of unrelated proteins and other biomolecules present in the cell environment can potentially mask the intended protein presentation. Recently surface-grafted peptoid-based polymer brushes, both neutral and zwitterionic, have emerged as candidate surfaces for resisting protein adsorption and anti-fouling applications due to their strong hydration and chain flexibility. On the other hand, specific peptoid sequences may also be prepared to enable specific protein binding interactions. However, molecular level insight into peptoid and brush interactions with proteins are both lacking. Using atomistic molecular dynamics simulation, we investigated the interaction of the fibronectin (Fn) FnIII9−10 domains, which exhibit fibronectin’s integrin cell adhesive motifs, with neutral polysarcosine and a sequence specific zwitterionic analog. As expected, peptoids simulated at different grafting densities exhibited protein adsorbing and antifouling regimes. however, comparison of independent adsorption simulations, including with different starting orientations of the protein, identified regions of FnIII9−10 that are typically involved in peptoid interactions, suggesting a degree of specificity in this. The binding regions were distinct from the integrin binding motifs and different interactions were observed between polysarcosine and the zwitterionic sequence. Unlike typical protein-surface adsorption, the specific interactions are driven by polar interactions. These observations give new insight into protein- surface interactions, which can be used to guide the development of new biomaterials.