Amphipathic helical peptide-Nile red probes for fluorescence probing of the lipid packing defects and their surrounding membranes on exosomes

Abstract Amphipathic helical (AH) peptide-based fluorescent probes were explored for analysis of lipid packing defects (LPDs) in the membrane surface of exosomes. Two kinds of AH peptide sequences, derived from the C-terminal sequence of Apolipoprotein A-I (ApoC) and from human α-synuclein (p2-23),...

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Main Authors: Yusuke Sato, Kazuya Segawa, Tomomi Sakamoto, Arihiro Narita, Kota Matsumoto, Seiichi Nishizawa
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-08534-w
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author Yusuke Sato
Kazuya Segawa
Tomomi Sakamoto
Arihiro Narita
Kota Matsumoto
Seiichi Nishizawa
author_facet Yusuke Sato
Kazuya Segawa
Tomomi Sakamoto
Arihiro Narita
Kota Matsumoto
Seiichi Nishizawa
author_sort Yusuke Sato
collection DOAJ
description Abstract Amphipathic helical (AH) peptide-based fluorescent probes were explored for analysis of lipid packing defects (LPDs) in the membrane surface of exosomes. Two kinds of AH peptide sequences, derived from the C-terminal sequence of Apolipoprotein A-I (ApoC) and from human α-synuclein (p2-23), were examined, where they differ in the hydrophobic face that can be inserted into LPDs. From the examination of the insertion depth of the AH peptides and the competitive binding using synthetic liposomes as exosome models, we found that ApoC peptide could serve as a binder for deep LPDs whereas p2-23 peptide preferentially recognizes shallow LPDs. These peptides conjugated with an environment-sensitive dye Nile Red (NR) were demonstrated to be useful for assessing both the abundance of target LPDs by the fluorescent enhancement response and the membrane properties surrounding these LPDs by the emission wavelength of the probes, respectively. With these properties, our probes successfully characterized the LPDs of exosomes from three kinds of cancer cells (A549, Hela and MCF7 cells). We showed that exosomal membranes exhibited unique structural properties regarding deep and shallow LPDs and their surrounding membrane polarity. In addition, these properties significantly depended on the donor cells. Our probes would serve as powerful tools for LPD analysis with a view toward a better understanding of exosomal membranes.
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spelling doaj-art-ccc4dbc07fe64ca1a243ef7e1c7798c52025-08-20T03:03:28ZengNature PortfolioScientific Reports2045-23222025-07-011511910.1038/s41598-025-08534-wAmphipathic helical peptide-Nile red probes for fluorescence probing of the lipid packing defects and their surrounding membranes on exosomesYusuke Sato0Kazuya Segawa1Tomomi Sakamoto2Arihiro Narita3Kota Matsumoto4Seiichi Nishizawa5Department of Chemistry, Graduate School of Science, Tohoku UniversityDepartment of Chemistry, Graduate School of Science, Tohoku UniversityDepartment of Chemistry, Graduate School of Science, Tohoku UniversityDepartment of Chemistry, Graduate School of Science, Tohoku UniversityDepartment of Chemistry, Graduate School of Science, Tohoku UniversityDepartment of Chemistry, Graduate School of Science, Tohoku UniversityAbstract Amphipathic helical (AH) peptide-based fluorescent probes were explored for analysis of lipid packing defects (LPDs) in the membrane surface of exosomes. Two kinds of AH peptide sequences, derived from the C-terminal sequence of Apolipoprotein A-I (ApoC) and from human α-synuclein (p2-23), were examined, where they differ in the hydrophobic face that can be inserted into LPDs. From the examination of the insertion depth of the AH peptides and the competitive binding using synthetic liposomes as exosome models, we found that ApoC peptide could serve as a binder for deep LPDs whereas p2-23 peptide preferentially recognizes shallow LPDs. These peptides conjugated with an environment-sensitive dye Nile Red (NR) were demonstrated to be useful for assessing both the abundance of target LPDs by the fluorescent enhancement response and the membrane properties surrounding these LPDs by the emission wavelength of the probes, respectively. With these properties, our probes successfully characterized the LPDs of exosomes from three kinds of cancer cells (A549, Hela and MCF7 cells). We showed that exosomal membranes exhibited unique structural properties regarding deep and shallow LPDs and their surrounding membrane polarity. In addition, these properties significantly depended on the donor cells. Our probes would serve as powerful tools for LPD analysis with a view toward a better understanding of exosomal membranes.https://doi.org/10.1038/s41598-025-08534-wFluorescent probeExosomeMembranesLipid packing defectPolarity
spellingShingle Yusuke Sato
Kazuya Segawa
Tomomi Sakamoto
Arihiro Narita
Kota Matsumoto
Seiichi Nishizawa
Amphipathic helical peptide-Nile red probes for fluorescence probing of the lipid packing defects and their surrounding membranes on exosomes
Scientific Reports
Fluorescent probe
Exosome
Membranes
Lipid packing defect
Polarity
title Amphipathic helical peptide-Nile red probes for fluorescence probing of the lipid packing defects and their surrounding membranes on exosomes
title_full Amphipathic helical peptide-Nile red probes for fluorescence probing of the lipid packing defects and their surrounding membranes on exosomes
title_fullStr Amphipathic helical peptide-Nile red probes for fluorescence probing of the lipid packing defects and their surrounding membranes on exosomes
title_full_unstemmed Amphipathic helical peptide-Nile red probes for fluorescence probing of the lipid packing defects and their surrounding membranes on exosomes
title_short Amphipathic helical peptide-Nile red probes for fluorescence probing of the lipid packing defects and their surrounding membranes on exosomes
title_sort amphipathic helical peptide nile red probes for fluorescence probing of the lipid packing defects and their surrounding membranes on exosomes
topic Fluorescent probe
Exosome
Membranes
Lipid packing defect
Polarity
url https://doi.org/10.1038/s41598-025-08534-w
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