Whole-GUV patch-clamping

Significance

Although membrane composition and tension modulate the activity of ion channels and transporters, this protein–membrane coupling has been challenging to study due to the difficulty of controlling membrane properties in cells and technical limitations of existing in vitro systems. This work demonstrates that the whole-cell patch-clamp technique is stabilized by a dynamic passivation mechanism that can be used to control and measure the current and voltage of intact giant unilamellar vesicles (GUVs), a cell-sized model biomimetic system in which the membrane composition, tension, and shape can be readily controlled. The resulting “whole-GUV” configuration will permit electrophysiological studies of ion channels and transporters in a membrane with a defined composition and physiologically relevant range of tensions.