Design and Biological Evaluation of hBest1-Containing Bilayer Nanostructures
Bestrophinopathies are a group of inherited retinal diseases caused by mutations in the <i>BEST1</i> gene. The protein encoded by this gene, bestorphin-1 (hBest1), is a calcium-dependent transmembrane channel localized on the basolateral membrane of retinal pigment epithelial (RPE) cells...
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MDPI AG
2025-07-01
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| author | Pavel Bakardzhiev Teodora Koleva Kirilka Mladenova Pavel Videv Veselina Moskova-Doumanova Aleksander Forys Sławomira Pusz Tonya Andreeva Svetla Petrova Stanislav Rangelov Jordan Doumanov |
| author_facet | Pavel Bakardzhiev Teodora Koleva Kirilka Mladenova Pavel Videv Veselina Moskova-Doumanova Aleksander Forys Sławomira Pusz Tonya Andreeva Svetla Petrova Stanislav Rangelov Jordan Doumanov |
| author_sort | Pavel Bakardzhiev |
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| description | Bestrophinopathies are a group of inherited retinal diseases caused by mutations in the <i>BEST1</i> gene. The protein encoded by this gene, bestorphin-1 (hBest1), is a calcium-dependent transmembrane channel localized on the basolateral membrane of retinal pigment epithelial (RPE) cells. We have already demonstrated the surface behavior and organization of recombinant hBest1 and its interactions with membrane lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM) and cholesterol (Chol) in models of biological membranes, which affect the hBest1 structure–function relationship. The main aim of our current investigation is to integrate pure hBest1 protein into lipid bilayer nanostructures. We synthesized and characterized various hBest1-containing nanostructures based on 1,2-Dipalmitoylphosphatidylcholine (DPPC), SM, glycerol monooleate (GMO) and Chol in different ratios and determined their cytotoxicity and incorporation into cell membranes and/or cells by immunofluorescence staining. Our results show that these newly designed nanoparticles are not cytotoxic and that their incorporation into MDCK II cell membranes (used as a model system) may provide a mechanism that could be applied to RPE cells expressing mutated hBest1 in order to restore their ion transport functions, affected by mutated and malfunctioning hBest1 molecules. |
| format | Article |
| id | doaj-art-15c7ae8f4bc54f26976de414f3a3958a |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-15c7ae8f4bc54f26976de414f3a3958a2025-08-20T03:56:49ZengMDPI AGMolecules1420-30492025-07-013014294810.3390/molecules30142948Design and Biological Evaluation of hBest1-Containing Bilayer NanostructuresPavel Bakardzhiev0Teodora Koleva1Kirilka Mladenova2Pavel Videv3Veselina Moskova-Doumanova4Aleksander Forys5Sławomira Pusz6Tonya Andreeva7Svetla Petrova8Stanislav Rangelov9Jordan Doumanov10Institute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Str. 103A, 1113 Sofia, BulgariaFaculty of Biology, Sofia University “St. Kliment Ohridski”, Dragan Tsankov Blvd., 1164 Sofia, BulgariaFaculty of Biology, Sofia University “St. Kliment Ohridski”, Dragan Tsankov Blvd., 1164 Sofia, BulgariaFaculty of Biology, Sofia University “St. Kliment Ohridski”, Dragan Tsankov Blvd., 1164 Sofia, BulgariaFaculty of Biology, Sofia University “St. Kliment Ohridski”, Dragan Tsankov Blvd., 1164 Sofia, BulgariaCentre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowskiej 34, 41-819 Zabrze, PolandCentre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowskiej 34, 41-819 Zabrze, PolandFaculty Life Sciences, Reutlingen University, Alteburgstraße 150, 72762 Reutlingen, GermanyFaculty of Biology, Sofia University “St. Kliment Ohridski”, Dragan Tsankov Blvd., 1164 Sofia, BulgariaInstitute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Str. 103A, 1113 Sofia, BulgariaFaculty of Biology, Sofia University “St. Kliment Ohridski”, Dragan Tsankov Blvd., 1164 Sofia, BulgariaBestrophinopathies are a group of inherited retinal diseases caused by mutations in the <i>BEST1</i> gene. The protein encoded by this gene, bestorphin-1 (hBest1), is a calcium-dependent transmembrane channel localized on the basolateral membrane of retinal pigment epithelial (RPE) cells. We have already demonstrated the surface behavior and organization of recombinant hBest1 and its interactions with membrane lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM) and cholesterol (Chol) in models of biological membranes, which affect the hBest1 structure–function relationship. The main aim of our current investigation is to integrate pure hBest1 protein into lipid bilayer nanostructures. We synthesized and characterized various hBest1-containing nanostructures based on 1,2-Dipalmitoylphosphatidylcholine (DPPC), SM, glycerol monooleate (GMO) and Chol in different ratios and determined their cytotoxicity and incorporation into cell membranes and/or cells by immunofluorescence staining. Our results show that these newly designed nanoparticles are not cytotoxic and that their incorporation into MDCK II cell membranes (used as a model system) may provide a mechanism that could be applied to RPE cells expressing mutated hBest1 in order to restore their ion transport functions, affected by mutated and malfunctioning hBest1 molecules.https://www.mdpi.com/1420-3049/30/14/2948hBest1bilayer nanostructuresMDCK II cells |
| spellingShingle | Pavel Bakardzhiev Teodora Koleva Kirilka Mladenova Pavel Videv Veselina Moskova-Doumanova Aleksander Forys Sławomira Pusz Tonya Andreeva Svetla Petrova Stanislav Rangelov Jordan Doumanov Design and Biological Evaluation of hBest1-Containing Bilayer Nanostructures Molecules hBest1 bilayer nanostructures MDCK II cells |
| title | Design and Biological Evaluation of hBest1-Containing Bilayer Nanostructures |
| title_full | Design and Biological Evaluation of hBest1-Containing Bilayer Nanostructures |
| title_fullStr | Design and Biological Evaluation of hBest1-Containing Bilayer Nanostructures |
| title_full_unstemmed | Design and Biological Evaluation of hBest1-Containing Bilayer Nanostructures |
| title_short | Design and Biological Evaluation of hBest1-Containing Bilayer Nanostructures |
| title_sort | design and biological evaluation of hbest1 containing bilayer nanostructures |
| topic | hBest1 bilayer nanostructures MDCK II cells |
| url | https://www.mdpi.com/1420-3049/30/14/2948 |
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