Inducing Biopolymer Folding via Responsive Nanoconfinement

Controlling the folding of biopolymers in crowded and confined environments (e.g., biological cells) remains a significant challenge. For example, crowding or confinement of proteins can influence transition pathways between folded and unfolded states. In experiments, polymers can be immersed in a solution of crowding agents or in a confined environment. One adaptive, stimuli-responsive medium for confinement can be offered by microgels – microscopic crosslinked polymer networks that swell by absorbing solvent and whose swelling behavior responds to changes in temperature [1]. To explore the influence of confinement on the structure of polymers and the surrounding medium, we model fluctuating conformations by probability distributions of gyration tensor eigenvalues [2] and microgels via the Flory-Rehner theory of polymer networks. Within this coarse-grained model, we perform molecular simulations of polymers in solutions of crowders and microgels and analyze polymer response (size, shape, and folding) to changes in crowder concentration and microgel swelling. Our results can elucidate protein behavior in crowded cellular environments.

[1] Routh et al., J. Phys. Chem. B 110, 12721 (2006).

[2] W. K. Lim and A. R. Denton, J. Chem. Phys. 141, 114909 (2014); 144, 024904 (2016).