Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 56, Issue 26, Pages 7644-7647Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201703578
Keywords
cell membranes; cell-penetrating peptides; di-4-ANEPPDHQ dye; lipid packing; oligoarginine
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Funding
- JSPS KAKENHI [JP26102522, JP15H02497, JP16H00763]
- PREST from Japan Science and Technology Agency (JST)
- JSPS
- Tohoku University Institute for Promoting Graduate Degree Programs Division for Interdisciplinary Advanced Research and Education
- Grants-in-Aid for Scientific Research [16H00763, 16J02319, 15K07955] Funding Source: KAKEN
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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.
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