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Published on: October 24, 2017
Thermal Stability of Phase-Separated Domains in Multicomponent Lipid Membranes with Local Anesthetics
Ko Sugahara1, Naofumi Shimokawa2, Masahiro Takagi3
1School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan. koblack0083@jaist.ac.jp.
Abstract:
The functional mechanisms of local anesthetics (LAs) have not yet been fully explained, despite their importance in modern medicine. Recently, an indirect interaction between channel proteins and LAs was proposed as follows: LAs alter the physical properties of lipid membranes, thus affecting the channel proteins. To examine this hypothesis, we investigated changes in thermal stability in lipid membranes consisting of dioleoylphosphocholine, dipalmitoylphosphocholine, and cholesterol by adding the LAs, lidocaine and tetracaine. The miscibility temperature of liquid-ordered (Lo) and liquid-disordered (Ld) phase separation was lowered, whereas that of phase separation between solid-ordered (So) and Ld phases was unchanged by LAs. Furthermore, we measured the line tension at the Lo/Ld interface from domain boundary fluctuation and found that it was significantly decreased by LAs. Finally, differential scanning calorimetry (DSC) revealed a change in the lipid main transition temperature on the addition of LAs. Based on the DSC measurements, we considered that LAs are partitioned into two coexisting phases.
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