Naslov
Mechanism of Cell Penetration by Permeabilization of Late Endosomes: Interplay between a Multivalent TAT Peptide and Bis(monoacylglycero)phosphate

Autori
Brock, Dakota J. ; Kondow-McConaghy, Helena ; Allen, Jason ; Brkljača, Zlatko ; Kustigian, Lauren ; Jiang, Mengqiu ; Zhang, Junjie ; Rye, Hays ; Vazdar, Mario ; Pellois, Jean-Philippe

Izvornik
Cell Chemical Biology (2451-9448) 27 (2020), 10; 1296-1307

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
cell-penetrating peptides ; endosomal escape ; cellular delivery ; membrane leakage ; bis(monoacylglycero)phosphate membrane fusion ; late endosomes

Sažetak
Many cellular delivery reagents enter the cytosolic space of cells by escaping the lumen of endocytic organelles and, more specifically, late endosomes. The mechanisms involved in endosomal membrane permeation remain largely unresolved, which impedes the improvement of delivery agents. Here, we investigate how 3TAT, a branched analog of the cell-penetrating peptide (CPP) TAT, achieves the permeabilization of bilayers containing bis(monoacylglycero)phosphate (BMP), a lipid found in late endosomes. We establish that the peptide does not induce the leakage of individual lipid bilayers. Instead, leakage requires contact between membranes. Peptide- driven bilayer contacts lead to fusion, lipid mixing, and, critically, peptide encapsulation within proximal bilayers. Notably, this encapsulation is a distinctive property of BMP that explains the specificity of CPP's membrane leakage activity. These results therefore support a model of cell penetration that requires both BMP and the vicinity between bilayers, two features unique to BMP-rich and multivesicular late endosomes.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA