Abstract

The electric potential at the interface of a lipid bilayer, known as the boundary potential (BP), is a critical determinant of membrane-protein interactions, ion transport, and overall cellular function. Despite its importance, the precise and reliable detection and interpretation of the BP, particularly its distinct surface and dipole components, remains a methodological challenge. This study addresses this gap by presenting the **first steps** toward a refined experimental and theoretical framework for analyzing the lipid membrane boundary potential. We employed a combination of advanced electrophysiological techniques, such as the Intramembranous Field Compensation (IFC) method on planar bilayer lipid membranes (BLM), alongside electrokinetic measurements on liposome suspensions. This dual approach allowed for the differential detection of changes in the surface potential, which is sensitive to charged species, and the dipole potential, which reflects the structural organization of the lipid headgroups. Key findings include the successful establishment of a robust protocol for separating these two components and the demonstration that the BP is highly sensitive to subtle changes in lipid composition and the presence of membrane-active agents. These results provide a foundational methodology for future biophysical studies, offering new insights into the molecular nature of the electric field at the membrane interface and its fundamental role in cellular processes.