Enzyme-induced kinetic control over self-assembly of amphiphilic surfactants

One of the main challenges with many pharmaceutical products is the severe side effects caused by the toxicity of drugs to the non-targeted parts of human bodies. Developing an effective controlled release approach would be a potential solution since it minimizes the interaction between the drug and the non-targeted sites. pH responsive micellar structures are heavily researched as drug delivery cargos as they undergo shape and permeability transitions in response to pH changes. However, the knowledge of such systems is imperfect regarding how dynamic changes in pH affect the immediate structures and sizes, which is a quite common scenario in biological organisms. Inspired by some recent experimental observations, we modeled a pH responsive system of O-methyl-serine-dodecylamide hydrochloride (MSDH) solution with urea/urease catalytic reaction as the pH controller. We first used coarse-grained molecular dynamics (CGMD) to simulate the morphologies of MSDH at different pH conditions. Having established the equilibrium self-assembly behavior, we performed a series of in silico tests of pseudo-reaction by applying step-wise perturbations in pH, where we observe qualitatively different structures due to kinetic effects. Finally, we compared several time scales involved in the self-assembly process and discussed possible mechanisms of forming kinetically driven structures. The results could be potentially helpful in developing state-of-art drug delivery systems.