A direct biocombinatorial strategy towards next generation, mussel-glue inspired saltwater adhesives.

Patrick Wilkea, Nicolas Helfrichtb, Andreas Markb, Georg Papastavroub, Damien Faivrec and Hans G. Börnera*

a)Humboldt-Universität zu Berlin, Department of Chemistry, Laboratory for organic synthesis of functional systems, D-12489 Berlin, Germany.

b)University of Bayreuth, Physical Chemistry II, D-95440 Bayreuth, Germany
c)Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, Science Park Golm, D-14424 Potsdam, Germany

Abstract: Biological materials exhibit remarkable, purpose-adapted properties that provide source of inspiration for designing new materials to meet the requirements of future applications. For instance, marine mussels are able to attach to a broad spectrum of hard surfaces under hostile conditions. Controlling wet-adhesion of synthetic macromolecules by analogue processes promises to strongly impact materials sciences by offering advanced coatings, adhesives and glues. The de novo design of macromolecules to mimic complex aspects of mussel adhesion still constitutes a challenge. Phage display allows material scientists to design specifi-cally interacting molecules with tailored affinity to material surfaces. Here, we report on the integration of enzymatic processing steps into phage display biopanning to expand the biocombinatorial procedure and enable the direct selection of enzymatically activable peptide adhesion domains. Adsorption isotherms and single molecule force spectroscopy show that those de novo peptides mimic complex aspects of bioadhesion, such as enzymatic activation (by tyrosinase), the switchability from weak to strong binders and adsorption under hostile saltwater conditions. Furthermore, peptide-poly(ethylene oxide) conjugates are synthesized to generate protective coatings, which possess antifouling properties and suppress irreversible interactions with blood-plasma protein cocktails. The extended phage display procedure provides a generic way to non-natural peptide adhesion domains, which not only mimic nature but improve biological sequence sections extractable from mussel-glue proteins. The de novo peptides manage to combine several tasks in a minimal 12mer sequence and thus pave the way to overcome major challenges of technical wet-glues.