The membrane translocation efficiency of Cell Penetrating Peptides (CPPs) has been largely studied, and poly-arginines have been highlighted as particularly active CPPs, especially upon negatively charged membranes. Here we inquire about the influence of membrane mechanical properties in poly-arginine adsorption, penetration and translocation, as well as the subsequent effect on the host membrane. For this, we selected anionic membranes exhibiting different rigidity and fluidity, and exposed them to the nona-arginine KR9C. Three different membrane compositions were investigated, all of them having 50% of the anionic lipid DOPG, thus ensuring a high affinity of the peptide for membrane surfaces. The remaining 50% was a saturated PC (DPPC), an unsaturated PC (DOPC) or a mixture of DOPC with cholesterol. Peptide-membrane interactions were studied using four complementary models for membranes: Langmuir monolayers, Large Unilamellar Vesicles, Black Lipid Membranes and Giant Unilamellar Vesicles. The patterns of interaction of KR9C varied within the different membrane compositions. The peptide strongly adsorbed on membranes with cholesterol, but did not incorporate or translocate them. KR9C stabilized phase segregation in DPPC/DOPG films and promoted vesicle rupture. DOPC/DOPG appeared as the better host for peptide translocation: KR9C adsorbed, inserted and translocated these membranes without breaking them, despite softening was observed. In cell membranes, a great variety of compositions coexist transiently in small patches, each one with different mechanical properties. Thus, pre-concentration of CPP may occur in a region enriched in cholesterol, whilst the peptide inserts in a neighbor region depleted of cholesterol. Under this point of view, the patchwork like organization of the membrane would act synergistically enhancing peptide translocation.

Interaction of a polyarginine peptide with membranes of different mechanical properties

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.