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Updated: Jan 11, 2026

From Fast Fluorescence Imaging to Molecular Diffusion Law on Live Cell Membranes in a Commercial Microscope
Published on: October 9, 2014
Single-Molecule and Super-Resolution Diffusion Quantification Unveils Reversible Enhancement of Lipid-Membrane
Tyler Jepson1,2, Hansen Jin1,2, Chun Ying Wu1,2
1Department of Chemistry, University of California, Berkeley, California 94720, United States.
Abstract:
The molecular mechanism of general anesthesia remains a mystery. While many small molecules, ranging from xenon to diethyl ether, act as general anesthetics, few similarities exist in their chemical structures or properties. Utilizing single-molecule displacement/diffusivity mapping (SMdM), a diffusion-quantifying single-molecule and super-resolution microscopy tool, we unveil that at clinical concentrations, general anesthetics rapidly and reversibly enhance the lateral diffusivity of both model lipid bilayers and live-cell plasma membranes in a dose-dependent fashion based on the anesthetic potency. With in situ fluorescence microscopy, we next show that the partitioning of anesthetics into the lipid bilayer causes fast dilation and area expansion. Employing a liposome-based fluorescence quenching assay, we further unveil enhanced lipid-bilayer permeability to the chloride ion (Cl-) in an anesthetic-concentration-dependent fashion. Together, our results indicate that the reversible insertion of anesthetic molecules into the lipid bilayer enhances the diffusivity and permeability of the lipid membrane, thus compromising neural functions.
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