Membrane transport modulates the pH-regulated feedback of an enzyme reaction confined within lipid vesicles

Understanding ion transport dynamics in reactive vesicles is pivotal for exploring biological and chemical processes and essential for designing synthetic cells. In this work, we investigate how proton transport and membrane potential regulate pH dynamics in an autocatalytic enzyme reaction within lipid vesicles. Combining experimental and numerical methods, we demonstrate that compartmentalization within lipid membranes accelerates internal reactions, attributed to protection from the external acidic environment. In experiments, we explored how proton movement significantly impacts internal reactions by changing bilayer thickness, adding ion transporters, and varying buffers. Numerical investigations incorporated electrical membrane potential and capacitance into a kinetic model of the process, elucidating the mechanisms that dictate the control of reaction time observed in the experiment, driven by both electrical and chemical potential gradients. These findings establish a framework for controlling pH clock reactions via membrane changes and targeted manipulation of proton movement, which could aid in the design of synthetic cells with precise, controlled functionalities.