Designing Single Chain Nanoparticles to Mimic Proteins

Proteins are the workhorses of living organisms and operate with near-perfect precision under native conditions, but their stability diminishes when subjected to subtle environmental perturbations. In contrast to proteins, their synthetic polymer analogs suffer from weak sequence and structural control. Recently, methacrylate-based random heteropolymers (RHPs) have demonstrated the ability to maintain biomimetic functions, including catalysis, transport and chaperoning. I have demonstrated how RHPs achieve population-based protein-mimetic functions. In particular, I have uncovered the design rules to endow synthetic polymers with bio-like hydration frustration (HF) properties. HF is the magic behind the functionality of proteins that allows them to dehydrate and hydrate hydrophilic and hydrophobic residues at will. For methacrylate-based RHPs, I found that hydration frustration arises from the competition between monomer compatibility (e.g., Flory-Huggins interaction parameter) and solvent exposed surface energy. The repeated appearance of atomistic structural motifs, particularly the alpha-methyl group on the methacrylate backbone and the polyethylene glycol side groups, results in physicochemical synergies despite the inherent randomness of their sequences.