Angewandte Chemie - International Edition
Angewandte Chemie - International Edition
5 years ago

Loosening of Lipid Packing Promotes Oligoarginine Entry into Cells

Loosening of Lipid Packing Promotes Oligoarginine Entry into Cells
Sergii Afonin, Yasufumi Takahashi, Takeshi Fukuma, Kenichi Kawano, Tomo Murayama, Shiroh Futaki, Toshihiro Masuda, Tomoka Takatani-Nakase, Anne S. Ulrich, Hiroki Ida
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. Lipid packing states of live cell membranes were analyzed under conditions that promote membrane translocation of octaarginine (R8); that is, cholesterol depletion, treatment with curvature-inducing peptides or hydrophobic counteranions, and high R8 concentration. Confocal laser scanning microscopy with a polarity-sensitive fluorescent probe revealed that loose lipid packing is a key factor underlying these conditions.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201703578

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