Biomaterials and nano-assemblies composed of proteins and charged macromolecules find important applications as pharmaceutical formulations, biocatalysts, drug delivery vehicles, and cell-contacting substrates. Despite their prevalence, the influence of polyelectrolyte assembly on protein structure and function is not well understood. Indeed, the recent literature includes examples of polyelectrolyte-enhanced protein stability, as well as examples of diminished stability. We report here on the conformational stability of a short, beta hairpin forming model protein, in the presence of various charged polymers of biological origin (poly(amino acids) and polysaccharides), as measured using molecular dynamics simulation and circular dichroism experiment. We find the temperature dependent extent of beta hairpin structure to vary significantly with polymer hydrophobicity and hydrogen bonding ability, and seek to understand these findings within a simple statistical mechanical lattice model. These studies lend important insight into the design of optimal polymers for diverse biomaterial applications, as well as broader questions on biomolecular (un)folding under crowded or heterogeneous conditions.

Polyelectrolyte-based biomaterials: Influence on protein structural stability

ACS Spring 2022

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