Boosting wet adhesion of a genetically engineered glue from supercharged polypeptides employing a combination of computational and experimental methods

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Although adhesion in dynamic and wet environments of the body is of prime importance in clinical applications such as surgery, it is still a technical challenge. Natural marine organisms have provided inspiration to develop underwater glues that can amalgamate high mechanical stability and high flexibility to resist continuous mechanical stresses and high ionic strength as well as pH in the presence of dynamic fluids and surfaces. In spite of the intricate biological machinery and chemistry, the primary underlying mechanism for adhesion in marine organisms is based on complex coacervation – driven by electrostatic interactions, followed by maturation into a solid phase – driven by short-range interactions. Complex coacervation occurs upon mixing of two oppositely charged polyelectrolytes, which undergo a liquid-liquid phase transition. Synthetic polyelectrolytes and natural or recombinant proteins have been extensively investigated to mimic this natural mechanism. However, they often failed to deliver strong adhesion strengths under ambient conditions. This is mainly due to the low degree of structural tunability, including charge density and distribution or the precise adjustment of molecular interactions etc., which imped our understanding about adhesion at the molecular scale. To overcome these challenges, we introduce a family of sequence-defined supercharged polypeptides (SUPs) and investigate the structural requirements to enhance their adhesive performance. SUPs consist of a repetitive amino acid sequence containing one charged residue (X) in every repeat ((VPGXG)n X:lysine or arginine). Our goal is to show how altering the architecture and composition of SUPs affect their mechanical properties and to optimize these features to improve underwater adhesion. This requires a delicate balance, at several time- and length-scales, between different types of molecular interactions. The project is divided into three main objectives: (1) synthesis of SUPs and encoding different types of molecular interactions in their structures, (2) investigation of adhesion performance of SUP-based complex coacervates at macroscopic scale and (3) elucidating the adhesion mechanism at the molecular level and improving the adhesion by a repetitive feedback between synthesis, characterization and computer simulation. We are aiming for precisely controlling the molecular parameters of SUPs including molar mass, charge density and charge gradients, topology as well as chemistry to develop a comprehensive model and to predict the wet adhesion properties.