Impact of Molecular Architecture and Adsorption Density on Adhesion of Mussel-Inspired Surface Primers with Catechol-Cation Synergy

Abstract

Marine mussels secrete proteins rich in residues containing catechols and cationic amines that displace hydration layers and adhere to charged surfaces under water via a cooperative binding effect known as catechol-cation synergy. Mussel-inspired adhesives containing paired catechol and cationic functionalities are a promising class of materials for biomedical applications, but few studies address the molecular adhesion mechanism(s) of these materials. To determine whether intramolecular adjacency of these functionalities is necessary for robust adhesion, a suite of siderophore analog surface primers was synthesized with systematic variations in intramolecular spacing between catechol and cationic functionalities. Adhesion measurements conducted with a surface forces apparatus (SFA) allow adhesive failure to be distinguished from cohesive failure and show that the failure mode depends critically on the siderophore analog adsorption density. The adhesion of these molecules to muscovite mica in an aqueous electrolyte solution demonstrates that direct intramolecular adjacency of catechol and cationic functionalities is not necessary for synergistic binding. However, we show that increasing the catechol-cation spacing by incorporating nonbinding domains results in decreased adhesion, which we attribute to a decrease in the density of catechol functionalities. A mechanism for catechol-cation synergy is proposed based on electrostatically driven adsorption and subsequent binding of catechol functionalities. This work should guide the design of new adhesives for binding to charged surfaces in saline environments.

Cooperativity of Catechols and Amines in High‐Performance Dry/Wet Adhesives

“…Surprisingly, we did not observe a substantial increase in the dry and wet failure times as compared to PSA‐DAc. Unlike the behavior noted at the molecular level in this study and recent SFA measurements by others, the static shear test results indicate that close proximity of cation‐aromatic binding pairs can significantly affect the macroscopic cohesive strength. The results might also explain why marine mussels have evolved to secrete adhesive proteins with Dopa and Lys pairs located mostly adjacent to each other rather than separated by spacer amino acids such as glycine.…”

“…The trend observed in CPS measurements is similar to what was noted earlier in SMFS experiments and can indicate that architecture of the polymer and the adjacency of catechol‐ and amine‐containing groups might not be necessary in establishing the cooperative effects to improve the adhesion, at least when measured at the microscopic or molecular levels. Similar observations have been made recently by Degen et al., where results of SFA measurements implied that incorporating glycine residues as spacer between the cationic and catecholic groups did not lead to significant changes in the force required to separate peptide‐coated mica surfaces.…”

“…Since Lys and Dopa residues are most commonly positioned adjacent to each other along the backbone in Mfp‐3 and 5, it was initially hypothesized that the close proximity of the cationic Lys residues and catecholic motifs are necessary to establish the synergistic effects . However, recently it has been suggested that the adjacency of the two functional motifs might not be required for the synergistic effects and only co‐presence of cationic and catecholic groups might lead to major improvements in adhesive performance . To further test this notion we studied interfacial adhesion of PSA‐DAc‐ABA.…”

Molecular design principles of Lysine-DOPA wet adhesion

“…For instance, a large number of positively charged Lys or arginine (Arg) residues are found in proximity to DOPA along the protein backbone 23 . Recently, Maier et al and others utilized surface forces apparatus (SFA) to study the adaptive synergy between amine and catechol in binding to wet mica, using small molecule cyclic analogs with Lys or Arg present adjacent to catechol or phenyl groups 1,24,25 . Their results showed that adhesion energy is remarkably higher when both catechol and amine are present, suggesting a synergistic effect between these functional motifs.…”

Bioengineered Protein‐based Adhesives for Biomedical Applications

“…[24,25] It is known that the proteins secreted by various organisms such as mussels and sandcastle worms demonstrate robust adhesion performance under different conditions. [26][27][28][29][30][31] Through the analysis of their protein structures, large amount of 3,4-dihydroxy-L-phenylalanine (DOPA) moieties are found in these proteins that play a crucial role for their adhesion performance due to the diversity of catechol chemistry. [32][33][34][35][36] Traditionally, mussel foot proteins (Mfps) are extracted directly from mussel foot filaments, which is expensive owing to the high production costs and low extraction efficiency.…”