Effects of Polymer Architecture and Charged Molecular Crowders on Hydrophobic Polymer Collapse

Accounting for the crowding effects inside a living cell is crucial to obtain a comprehensive view of the biomolecular processes and designing responsive polymer-based materials for biomedical applications. These effects have long been synonymous with the entropic volume exclusion effects. The role of soft, attractive intermolecular interactions remains elusive. Here, we investigate the effects of model cationic and anionic hydrophobic molecular crowders on the collapse equilibrium of uncharged model polymers using molecular dynamics simulations. Particularly, the effect of polymer architecture is explored where a 50-bead linear polymer model (Poly-I) and a branched polymer model (Poly-II) with nonpolar side chains are examined. The collapse of Poly-I is found to be highly favorable than in Poly-II in neat water. Addition of anionic crowders strengthens hydrophobic collapse in Poly-I, whereas collapse of Poly-II is only slightly favored over that in neat water. The thermodynamic driving forces are quite distinct in water. Collapse of Poly-I is driven by the favorable polymer–solvent entropy change (due to loss of waters to bulk on collapse), whereas collapse of Poly-II is driven by the favorable polymer–solvent energy change (due to favorable intrapolymer energy). The anionic crowders support the entropic mechanism for Poly-I by acting like surfactants, redirecting water dipoles toward themselves, and preferentially adsorbing on the Poly-I surface. In the case of Poly-II, the anionic crowders are loosely bound to polymer side chains, and loss of crowders and waters to the bulk on polymer collapse reduces the entropic penalty, thereby making collapse free energy slightly more favorable than in neat water. The results indicate the discriminating behavior of anionic crowders to strengthen the hydrophobic collapse. It is related to the structuring of water molecules around the termini and the central region of the two polymers. The results address the modulation of hydrophobic hydration by weakly hydrated ionic hydrophobes at crowded concentrations.