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

ABSTRACT: 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 (R₉)-mediated membrane reorganization that facilitates the translocation of peptides across laterally heterogeneous membranes is directly visualized. The electrostatic binding of cationic R₉ to anionic phosphatidylserine (PS)-enriched domains on a freestanding lipid bilayer induces lateral lipid rearrangements; in particular, in real-time it is observed that R₉ fluidizes PS-rich liquid-ordered (L_o) domains into liquid-disordered (L_d) domains, resulting in the membrane permeabilization. The experiments with

SUBMITTER: Park S 

PROVIDER: S-EPMC11348069 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature