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Molecular analysis of the interactions of the cell-penetrating peptide Penetratin and lipid membranes. Contributions of the lipid PIP2, biophysical approaches and benzophenone photoreactivity in model membranes

Abstract : Cell-penetrating peptides (CPP) can cross cell membranes and deliver biologically active molecules into cells. Previous work showed that CPPs could remodel the actin cytoskeleton, interacted strongly with negatively charged lipids and PIP2 could play a role in Penetratin internalization. Our DSC experiments showed that Penetratin interacts with polar head groups and impacts the lipid bilayer fluidity of PIP2-containing liposomes. It indicated that presence of PIP2 in liposomes triggers Penetratin-lipid interaction. Moreover, Penetratin binding affinity for PIP2-containing lipid vesicles, estimated by tryptophan fluorescence, pointed out that Penetratin has a higher affinity for PIP2 than for PS. Affinity photocrosslinking coupled to mass spectrometry, using benzophenone (Bzp)-functionalized peptides, was used to study the non-covalent interactions of CPPs and lipid membranes at a molecular level. PIP2 was found to be a good interaction partner for Penetratin and was preferably labelled in liposomes containing PC, PS and PIP2. We revealed highly informative secondary reactions occurring during UV irradiation that can occur concomitantly in a single biological system: a membrane-active peptide inserted within a phospholipid bilayer. This work shows how to exploit in an original way the different reactivities of Bzp in the context of a lipid membrane, giving access to information on the CPP/lipid interaction at a molecular level such as depth of insertion or membrane fluidity in the CPP vicinity.
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Submitted on : Monday, October 18, 2021 - 1:01:24 AM
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  • HAL Id : tel-03381780, version 1

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Leïla Bechtella. Molecular analysis of the interactions of the cell-penetrating peptide Penetratin and lipid membranes. Contributions of the lipid PIP2, biophysical approaches and benzophenone photoreactivity in model membranes. Biochemistry [q-bio.BM]. Sorbonne Université, 2019. English. ⟨NNT : 2019SORUS045⟩. ⟨tel-03381780⟩

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