@article{bebfdbfab36946a6b55c6b54e0c92262,
title = "Loosening of Lipid Packing Promotes Oligoarginine Entry into Cells",
abstract = "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.",
keywords = "cell membranes, cell-penetrating peptides, di-4-ANEPPDHQ dye, lipid packing, oligoarginine",
author = "Tomo Murayama and Toshihiro Masuda and Sergii Afonin and Kenichi Kawano and Tomoka Takatani-Nakase and Hiroki Ida and Yasufumi Takahashi and Takeshi Fukuma and Ulrich, {Anne S.} and Shiroh Futaki",
note = "Funding Information: S.F. was supported by JSPS KAKENHI (Grant Numbers JP26102522, JP15H02497, JP16H00763). This work was partially supported by PREST from the Japan Science and Technology Agency (JST) for Y.T. Authors T.M. and H.I. are grateful for the JSPS Research Fellowship for Young Scientists. H.I. is also grateful for the support of a Grant-in-Aid of Tohoku University Institute for Promoting Graduate Degree Programs Division for Interdisciplinary Advanced Research and Education. We thank Prof. T. Morii and Dr. E. Nakata (Kyoto University) for their help with DSC analysis, K. Arima for synthesis of peptides, and Dr. T. Takeuchi for helpful discussions. Publisher Copyright: {\textcopyright} 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2017",
month = jun,
day = "19",
doi = "10.1002/anie.201703578",
language = "English",
volume = "56",
pages = "7644--7647",
journal = "Angewandte Chemie - International Edition",
issn = "1433-7851",
publisher = "John Wiley and Sons Ltd",
number = "26",
}