Monolayers of a tetrazine-containing gemini amphiphile: Interplays with biomembrane lipids.

The property of a newly synthesized tetrazine derivative comprised of double C18-saturated hydrocarbon chain (C18-rTz-C18) has been studied in situ at the air-water interface. C18-rTz-C18 or a gemini amphiphile contributes to restriction of its tetrazine moiety on the interface, which is expected to be used for bioimaging and analytical reagents. Herein, to understand lateral interactions between Tz and biomembrane constituents, we investigated the interfacial behavior of Langmuir monolayers composed of C18-rTz-C18 and biomembrane lipids such as DPPC, DPPG, DPPE, PSM, and Cholesterol (Ch). The lateral interaction of the binary monolayers was analyzed with the surface pressure (π)-molecular area (A) and surface potential (ΔV)-A isotherms. These thermodynamic data indicate that all of the two-components are miscible with each other. In particular, as opposed to the others, the monolayer stability of DPPE, which is a major constituent of the inner surface of cell membranes, is attenuated by the small-amount addition of C18-rTz-C18. This specific interaction implies the membrane destruction from the inside. The phase behavior during monolayer compression was visualized with Brewster angle microscopy (BAM), fluorescence microscopy (FM), and atomic force microscopy (AFM). The obtained morphologies exhibit a coexistence state of two different liquid-condensed domains derived from extra phospholipids and phospholipids-C18-rTz-C18 monolayers.