Polymer folding in confined and crowded environments

A flexible homopolymer chain with sufficiently short-range interactions undergoes a first-order-like transition from an expanded coil to a compact crystallite analogous to the all-or-none folding exhibited by many small proteins [1]. Here we investigate this polymer folding transition under geometric confinement and in the presence of macromolecular crowders. One anticipates that both confinement and crowding will lead to entropic stabilization of the folded state. We use a Wang-Landau simulation approach to construct the partition function of a flexible square-well-sphere chain (monomer size d) that is (A) confined within a hard-wall slit [2] and (B) immersed in a hard-sphere solvent with solvent size D ≥ d and solvent volume fraction 0 < vf ≤ 0.4 [3]. Entropic stabilization is found in all cases. For the confined chain, isothermal reduction of the slit width can induce folding, unfolding, or crystallite restructuring. In the crowded environment an isothermal increase in the crowder density can induce folding. This crowding behavior is sensitive to the size of the crowder with larger crowders producing a smaller effect. [1] J. Chem. Phys. 145, 174903 (2016); [2] Macromolecules 50, 6967 (2017); [3] J. Chem. Phys. 147, 166101 (2017).