Design and synthesis of sphingomyelin-cholesterol conjugates and their formation of ordered membranes

Nobuaki Matsumori, Norio Tanada, Kohei Nozu, Hiroki Okazaki, Tohru Oishi, Michio Murata

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


A lipid raft is a cholesterol (Chol)-rich microdomain floating in a sea of lipid bilayers. Although Chol is thought to interact preferentially with sphingolipids such as sphingomyelin (SM), rather than with glycerophospholipids, the origin of the specific interaction has remained unresolved, primarily because of the high mobility of lipid molecules and weak intermolecular interactions. In this study, we synthesized SM-Chol conjugates with functionally designed linker portions to restrain Chol mobility and examined their formation of ordered membranes by a detergent insolubility assay, fluorescence anisotropy experiments, and fluorescence-quenching assay. In all of the tests, membranes prepared from the conjugates showed properties of ordered domains comparable to a SM-Chol (1:1) membrane. To gain insight into the structure of bilayers composed from the conjugates, we performed molecular dynamics simulations with 64 molecules of the conjugates, which suggested that the conjugates form a stable bilayer structure by bending at the linker portion and, mostly, reproduce the hydrogen bonds between the SM and Chol portions. These results imply that the molecular recognition between SM and Chol in an ordered domain is essentially reproduced by the conjugated molecules and, thus, demonstrates that these conjugate molecules could potentially serve as molecular probes for understanding molecular recognition in lipid rafts.

Original languageEnglish
Pages (from-to)8568-8575
Number of pages8
JournalChemistry - A European Journal
Issue number31
Publication statusPublished - Jul 25 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Catalysis
  • Organic Chemistry


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