Surface force measurements and simulations of mussel-derived peptide adhesives on wet organic surfaces

Abstract

Translating sticky biological molecules-such as mussel foot proteins (MFPs)-into synthetic, cost-effective underwater adhesives with adjustable nano-and macroscale characteristics requires an intimate understanding of the glue's molecular interactions. To help facilitate the next generation of aqueous adhesives, we performed a combination of surface forces apparatus (SFA) measurements and replicaexchange molecular dynamics (REMD) simulations on a synthetic, easy to prepare, Dopa-containing peptide (MFP-3s peptide), which adheres to organic surfaces just as effectively as its wild-type protein analog. Experiments and simulations both show significant differences in peptide adsorption on CH 3 -terminated (hydrophobic) and OH-terminated (hydrophilic) self-assembled monolayers (SAMs), where adsorption is strongest on hydrophobic SAMs because of orientationally specific interactions with Dopa. Additional umbrella-sampling simulations yield free-energy profiles that quantitatively agree with SFA measurements and are used to extract the adhesive properties of individual amino acids within the context of MFP-3s peptide adhesion, revealing a delicate balance between van der Waals, hydrophobic, and electrostatic forces.mussel foot proteins | self-assembled monolayers | protein folding | molecular dynamics simulations | surface forces apparatus D emand for biologically inspired underwater adhesives, such as those secreted by marine mussels to adhere to a wide variety of hard and soft surfaces (1), have seen tremendous growth over the past decade, with applications to bone sealing (2), dental and medical transplants (3), coronary artery coatings (4), cell encapsulants (5), and other systems. To facilitate the construction of nextgeneration underwater adhesives, we can mimic existing biological glues-such as those containing mussel foot proteins (MFPs)-and translate the glues' structures to create biologically inspired synthetic adhesives (6). Doing so requires detailed knowledge of the molecular interactions that take place, many of which occur on length and time scales that are, at present, too small to be accurately characterized by experiments. Therefore, more sophisticated studies that combine theoretical modeling with state-of-the-art experiments are necessary for advancing the development of novel underwater adhesives.Although the mussel's talent for wet adhesion has been known for centuries, the true molecular understanding of adhesion began in 1952 with Brown's hypothesis that the mussel's byssus thread and adhesive plaques are comprised of intrinsically disordered proteins rich in the catecholic amino acid dopa (Dopa) (7). With knowledge of Dopa's binding ability, an abundance of Dopa-containing polymers were synthesized that displayed impressive adhesive (8, 9), coating (1, 4), structural (10, 11), and selfhealing (12, 13) properties. The surface forces apparatus (SFA) has been used to measure the adhesion of MFP-containing glues (1, 6, 14-17); however, it remains difficult to unambiguously identify individual or ...

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