Dueling Backbones: Comparing Peptoid and Peptide Analogues of a Mussel Adhesive Protein

Abstract

Ensembles of amino acid side chains often dominate the interfacial interactions of intrinsically disordered proteins; however, backbone contributions are far from negligible. Using a combination of nanoscale force measurements and molecular dynamics simulations, we demonstrated with analogous mussel-mimetic adhesive peptides and peptoids both 34 residues long that highly divergent adhesive/cohesive outcomes can be achieved on mica surfaces by altering backbone chemistry only. The Phe, Tyr, and Dopa containing peptoid variants used in this study deposited as dehydrated and incompressible films that facilitated analysis of peptoid side chain contributions to adhesion and cohesion. For example, whereas Phe and Dopa peptoids exhibited similar cohesion, Dopa peptoids were ∼3 times more adhesive than Phe peptoids on mica. Compared with the peptides, Phe peptoid achieved only ∼20% of Phe containing peptide adhesion, but the Dopa peptoids were >2-fold more adhesive than the Dopa peptides. Cation−π interactions accounted for some but not all of the cohesive interactions. Our results were corroborated by molecular dynamics simulations and highlight the importance of backbone chemistry and the potential of peptoids or peptoid/ peptide hybrids as wet adhesives and primers.

An Artificial Phase‐Transitional Underwater Bioglue with Robust and Switchable Adhesion Performance

“…Recently increasing research interests have been focused on natural bioadhesives particularly in contexts of biotechnology and materials science owing to their wet adhesion property,cytocompatibility,and biodegradability. [1][2][3][4] In native aquatic organisms such as mussels and sandcastle worms, soluble proteins with opposite charges present at ypical liquid-liquid phase separation, termed complex coacervation, showing wet adhesion performance. [5,6] Inspired by these natural-born adhesive systems,afew attempts for construction of artificial wet bioadhesives are explored.…”

Liquid–Liquid Phase Separation of the Green Mussel Adhesive Protein Pvfp‐5 is Regulated by the Post‐Translated Dopa Amino Acid

“…Dopa associated bidentate H‐bonding has previously been proposed for MFPs‐derived peptides and peptoids. [ 28,39 ] Our data indicate that this H‐bonding network configuration, whereby the two hydroxyl groups of one Dopa residue interact with one hydroxyl group positioned on Cε 2 of a second Dopa residue (Figure 5c) might be one of the dominant molecular configurations mediating sticker‐to‐sticker (attractive) interactions during LLPS of Pvfp‐5‐Dopa. In contrast, this stabilizing triangular configuration is not possible for Tyr because one OH group is not sufficient to create this tripartite H‐bonding network.…”

An Artificial Phase‐Transitional Underwater Bioglue with Robust and Switchable Adhesion Performance

“…Recently increasing research interests have been focused on natural bioadhesives particularly in contexts of biotechnology and materials science owing to their wet adhesion property, cytocompatibility, and biodegradability [1–4] . In native aquatic organisms such as mussels and sandcastle worms, soluble proteins with opposite charges present a typical liquid‐liquid phase separation, termed complex coacervation, showing wet adhesion performance [5, 6] .…”