Loosening of Lipid Packing Promotes Oligoarginine Entry into Cells

Tomo Murayama, Toshihiro Masuda, Sergii Afonin, Kenichi Kawano, Tomoka Takatani-Nakase, Hiroki Ida, Yasufumi Takahashi, Takeshi Fukuma, Anne S. Ulrich, Shiroh Futaki

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Despite extensive use of arginine-rich cell-penetrating peptides (CPPs)—including octaarginine (R8)—as intracellular delivery vectors, mechanisms for their internalization are still under debate. Lipid packing in live cell membranes was characterized using a polarity-sensitive dye (di-4-ANEPPDHQ), and evaluated in terms of generalized polarization. Treatment with membrane curvature-inducing peptides led to significant loosening of the lipid packing, resulting in an enhanced R8 penetration. Pyrenebutyrate (PyB) is known to facilitate R8 membrane translocation by working as a hydrophobic counteranion. Interestingly, PyB also actively induced membrane curvature and perturbed lipid packing. R8 is known to directly cross cell membranes at elevated concentrations. The sites of R8 influx were found to have looser lipid packing than surrounding areas. Lipid packing loosening is proposed as a key factor that governs the membrane translocation of CPPs.

Original languageEnglish
Pages (from-to)7644-7647
Number of pages4
JournalAngewandte Chemie - International Edition
Issue number26
Publication statusPublished - 2017 Jun 19
Externally publishedYes


  • cell membranes
  • cell-penetrating peptides
  • di-4-ANEPPDHQ dye
  • lipid packing
  • oligoarginine

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)


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