An octanol hinge opens the door to water transport

Abstract

Despite their prevalent use as a surrogate for partitioning of pharmacologically active solutes across lipid membranes, the mechanism of transport across water/octanol phase boundaries has remained unexplored. Using molecular dynamics, graph theoretical, cluster analysis, and Langevin dynamics, we reveal an elegant mechanism for the simplest solute, water. Self-assembled octanol at the interface reversibly binds water and swings like the hinge of a door to bring water into a semi-organized second interfacial layer (a “bilayer island”). This mechanism is distinct from well-known lipid flipping and water transport processes in protein-free membranes, highlighting important limitations in the water/octanol proxy. Interestingly, the collective and reversible behavior is well-described by a double well potential energy function, with the two stable states being the water bound to the hinge on either side of the interface. The function of the hinge for transport, coupled with the underlying double well energy landscape, is akin to a molecular switch or shuttle that functions under equilibrium and is driven by the differential free energies of solvation of H₂O across the interface. This example successfully operates within the dynamic motion of instantaneous surface fluctuations, a feature that expands upon traditional approaches toward controlled solute transport that act to avoid or circumvent the dynamic nature of the interface.