Supramolecular Mechanosensitive Potassium Channel Formed by Fluorinated Amphiphilic Cyclophane

• Published in: Journal of the American Chemical Society Vol. 144; no. 26; pp. 11802 - 11809
• Main Authors: Sato, Kohei, Sasaki, Ryo, Matsuda, Ryoto, Nakagawa, Mayuko, Ekimoto, Toru, Yamane, Tsutomu, Ikeguchi, Mitsunori, Tabata, Kazuhito V., Noji, Hiroyuki, Kinbara, Kazushi
• Format: Journal Article
• Language: English
• Published: American Chemical Society 06.07.2022
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.2c04118

Inspired by mechanosensitive potassium channels found in nature, we developed a fluorinated amphiphilic cyclophane composed of fluorinated rigid aromatic units connected via flexible hydrophilic octa­(ethylene glycol) chains. Microscopic and emission spectroscopic studies revealed that the cyclophane could be incorporated into the hydrophobic layer of the lipid bilayer membranes and self-assembled to form a supramolecular transmembrane ion channel. Current recording measurements using cyclophane-containing planer lipid bilayer membranes successfully demonstrated an efficient transmembrane ion transport. We also demonstrated that the ion transport property was sensitive to the mechanical forces applied to the membranes. In addition, ion transport assays using pH-sensitive fluorescence dye revealed that the supramolecular channel possesses potassium ion selectivity. We also performed all-atom hybrid quantum-mechanical/molecular mechanical simulations to assess the channel structures at atomic resolution and the mechanism of selective potassium ion transport. This research demonstrated the first example of a synthetic mechanosensitive potassium channel, which would open a new door to sensing and manipulating biologically important processes and purification of key materials in industries.