Arginine-Rich Cell-Penetrating Peptides Induce Lipid Rearrangements for Their Active Translocation across Laterally Heterogeneous Membranes.

Autor: Park S; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea., Kim J; Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea., Oh SS; Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.; Institute for Convergence Research and Education in Advanced Technology (I-CREATE), Yonsei University, Incheon, 21983, Republic of Korea., Choi SQ; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Aug; Vol. 11 (32), pp. e2404563. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1002/advs.202404563
Abstrakt: Arginine-rich cell-penetrating peptides (CPPs) have emerged as valuable tools for the intracellular delivery of bioactive molecules, but their membrane perturbation during cell penetration is not fully understood. Here, nona-arginine (R 9 )-mediated membrane reorganization that facilitates the translocation of peptides across laterally heterogeneous membranes is directly visualized. The electrostatic binding of cationic R 9 to anionic phosphatidylserine (PS)-enriched domains on a freestanding lipid bilayer induces lateral lipid rearrangements; in particular, in real-time it is observed that R 9 fluidizes PS-rich liquid-ordered (L o ) domains into liquid-disordered (L d ) domains, resulting in the membrane permeabilization. The experiments with giant unilamellar vesicles (GUVs) confirm the preferential translocation of R 9 through L d domains without pore formation, even when L o domains are more negatively charged. Indeed, whenever R 9 comes into contact with negatively charged L o domains, it dissolves the L o domains first, promoting translocation across phase-separated membranes. Collectively, the findings imply that arginine-rich CPPs modulate lateral membrane heterogeneity, including membrane fluidization, as one of the fundamental processes for their effective cell penetration across densely packed lipid bilayers.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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