Designing sequential functionality into polypeptide side-chains to mimic complex biopolymers

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

Non-Technical Abstract The prolific adhesive capabilities of many marine organisms are well known. Each year a considerable amount of time and money is spent worldwide on the removal of barnacles from fouled vessels and other man-made structures exposed to the oceans. The adhesive proteins produced by many permanently attached marine organisms are remarkable in that they can function over wide temperature ranges, fluctuating salinity, humidity, and in the tides, waves and currents of marine environments. In contrast, the success of man-made adhesives in wet environments requires carefully cleaned surfaces which often must also be chemically treated and/or partially dried. Marine adhesives have also been explored for use as tissue glues in surgery and in dentistry, yet they are expensive to produce and can cause immune reactions. This project will develop simplified mimics of marine adhesives to identify the key components and processes require for the design and synthesis of superior adhesives for wet environments. The concepts developed in this proposal have potential to be further utilized to prepare degradable, synthetic polypeptide materials for downstream wet adhesion applications in areas such as medicine and dentistry. This funding will also be used to recruit and train women and underrepresented minority students in chemistry and materials research to contribute strongly to the STEM workforce. Technical Abstract The performance and complexity of the proteins that are key polymeric components in marine mussel adhesives have received considerable attention in the past few decades. In addition to substantial efforts to study and decipher the biological processes, there has also been much effort to replicate mussel adhesive proteins (MAPs) using synthetic polymers. Synthetic polymers for wet adhesive applications offer potential advantages over biologically sourced proteins in terms of scalable production at low cost, absence of biological contaminants, and in some cases, improved properties for applications in medicine or industry. Many of these polymers have focused primarily on mimicking the 3,4-dehydroxyphenyl-L-alanine content of mussel proteins, but have paid less attention to many other functional groups and features of MAPs, such as hydrophobic and charged groups, as well as physical and chemical changes resulting from shifts in solution pH and redox potential. Although some efforts have attempted to mimic most if not all of these features in synthetic polymers, this remains a challenging problem, especially with respect to retaining amino acid sequence information and compositional uniformity. In this project, a new approach is proposed to address this challenge by mimicking MAP sequence information using uniform side-chain peptide sequences attached to homopolypeptide scaffolds designed to contain additional biomimetic functionality. The proposed studies aim to increase the level of functional sophistication in synthetic polymers closer toward true mimicry of the complexity found in multifunctional proteins. Knowledge gained from these studies will also yield scalable synthetic methods and design rules that can be applied to mimicry of other sequence specific protein materials. Outreach objectives in this proposal will continue current efforts developed by the PI in previous NSF-funded broader impacts in preparing women and underrepresented minority students for the STEM workforce. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.