Coacervate formation in amino acid functionalized polypeptides

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Coacervation is a process by which attractive electrostatic forces between positive and negative groups on long macromolecules called polyelectrolytes cause their aggregation and separation out of a mixture with water as a polyelectrolyte coacervate. These coacervates have similarities to cellular organelles that contain intrinsically disordered proteins and are not encapsulated in a membrane, hence their being named "membraneless organelles". Protein coacervates have been linked to many important biological processes and are also known to be key components of moisture-resistant adhesives produced by marine organisms, which have applications in medicine as surgical sealants. There is also considerable interest in use of coacervation to create materials that can be used as drug carriers, cell scaffolds, or for engineering applications. The research group of Professor Timothy Deming at University of California Los Angeles is developing a new class of coacervate-forming polypeptides, which are synthetic mimics of natural proteins and whose properties can be rapidly tuned for specific uses. The study of coacervate-forming polypeptides can be used in the efforts to better mimic and understand the physical behavior of disordered proteins and to prepare bioadhesives and biologically-inspired artificial organelles. This project is also contributing to the development of human resources in science, technology, engineering and mathematics. Specifically, the PI provides mentorship to the members of the International Society for Pharmaceutical Engineering Student Chapter at UCLA. He also trains bioengineering undergraduate students who work on interdisciplinary projects in an engineering lab and who have a medical school collaborator. The PI mentors in research high school students who participate in the Engineering Science Corps Outreach Program of the UCLA School of Engineering. This summer research program is designed to bring local underrepresented minority students from the LA area in research labs at UCLA where they learn about, and prepare for, careers in engineering.This project is focused on the (i) design, preparation and characterization of polypeptides whose sidechains makes them good mimics of coacervate-forming proteins and allows their properties to be tuned or switched, and on the (ii) design, preparation and characterization of block co-polypeptides that contain distinct hydrophilic and alpha-helical coacervate-forming domains and can form hydrogels responsive to environmental stimuli, such as the temperature and pH. The research team works to identify the molecular parameters that control the response of the molecules to temperature and pH. A pioneering aspect of this research is that the block copolypeptides can have multiple individual chain segments, each sensitive to temperature, ion, or redox changes; hence combinations of stimuli can generate different responses in the assemblies. The proposed materials are designed to form hydrogels. The material's ability to respond to environmental stimuli confers them potential utility in biology.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.