A Novel Voltage-sensing Nano-device based on Flexoelectric Coupling in Lipid Membranes

The sensing of transmembrane (TM) voltage differences (ΔVTM) is indispensable to key cellular functions executed by ion channels such as energy storage, signal transmission in nerves, the beating of the heart, and the sensation of heat, pain and hearing. The mechanism of voltage-sensing has been intensely investigated, and a consensus has emerged that charged voltage-sensing molecular motifs in proteins move in response to changes in ΔVTM, thus opening or closing the channel. Here, we break from tradition to propose that ion channels employ a second mechanism to sense ΔVTM, which exploits “flexoelectricity” in membranes. The concept of flexoelectricity dictates that in systems with orientational order such as lipid membranes, electrical dipoles alter their orientation in response to an external electric field. Therefore, an ion channel can harness the rotation of a TM dipole, such as an α-helix, to generate torque and thereby sense ΔVTM. To our best knowledge, such a unique sensing mechanism has so far neither been investigated, nor discovered in biology. We propose to exploit flexoelectricity to design novel voltage nano-sensors that can (1) sense ΔVTM in model membrane systems and (2) lead to the discovery of similar voltagesensing motifs in proteins such as ion channels in biology. Our research can lead to the discovery of a previously unknown type of voltage-sensing mechanism in membrane proteins – and a nanosensor with potential biomedical applications.