Targeting cholesterol in a liquid-disordered environment by theonellamides modulates cell membrane order and cell shape

Yuko Arita, Shinichi Nishimura, Reiko Ishitsuka, Takuma Kishimoto, Junichi Ikenouchi, Kumiko Ishii, Masato Umeda, Shigeki Matsunaga, Toshihide Kobayashi, Minoru Yoshida

Research output: Contribution to journalArticle

12 Citations (Scopus)


Roles of lipids in the cell membrane are poorly understood. This is partially due to the lack of methodologies, for example, tool chemicals that bind to specific membrane lipids and modulate membrane function. Theonellamides (TNMs), marine sponge-derived peptides, recognize 3β-hydroxysterols in lipid membranes and induce major morphological changes in cultured mammalian cells through as yet unknown mechanisms. Here, we show that TNMs recognize cholesterol-containing liquid-disordered domains and induce phase separation in model lipid membranes. Modulation of membrane order was also observed in living cells following treatment with TNM-A, in which cells shrank considerably in a cholesterol-, cytoskeleton-, and energy-dependent manner. These findings present a previously unrecognized mode of action of membrane-targeting natural products. Meanwhile, we demonstrated the importance of membrane order, which is maintained by cholesterol, for proper cell morphogenesis.

Original languageEnglish
Pages (from-to)604-610
Number of pages7
JournalChemistry and Biology
Issue number5
Publication statusPublished - May 30 2015


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this