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CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells
Cholesterol is an essential component of cellular membranes regulating the structural integrity and fluidity of biological bilayers and cellular processes such as signal transduction and membrane trafficking. However, tools to investigate the role and dynamics of cholesterol in live cells are still...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196198/ https://www.ncbi.nlm.nih.gov/pubmed/34117357 http://dx.doi.org/10.1038/s42003-021-02252-5 |
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author | Matos, Anna L. L. Keller, Fabian Wegner, Tristan del Castillo, Carla Elizabeth Cadena Grill, David Kudruk, Sergej Spang, Anne Glorius, Frank Heuer, Andreas Gerke, Volker |
author_facet | Matos, Anna L. L. Keller, Fabian Wegner, Tristan del Castillo, Carla Elizabeth Cadena Grill, David Kudruk, Sergej Spang, Anne Glorius, Frank Heuer, Andreas Gerke, Volker |
author_sort | Matos, Anna L. L. |
collection | PubMed |
description | Cholesterol is an essential component of cellular membranes regulating the structural integrity and fluidity of biological bilayers and cellular processes such as signal transduction and membrane trafficking. However, tools to investigate the role and dynamics of cholesterol in live cells are still scarce and often show limited applicability. To address this, we previously developed a class of imidazolium-based cholesterol analogs, CHIMs. Here we confirm that CHIM membrane integration characteristics largely mimic those of cholesterol. Computational studies in simulated phospholipid bilayers and biophysical analyses of model membranes reveal that in biologically relevant systems CHIMs behave similarly to natural cholesterol. Importantly, the analogs can functionally replace cholesterol in membranes, can be readily labeled by click chemistry and follow trafficking pathways of cholesterol in live cells. Thus, CHIMs represent chemically versatile cholesterol analogs that can serve as a flexible toolbox to study cholesterol behavior and function in live cells and organisms. |
format | Online Article Text |
id | pubmed-8196198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81961982021-06-17 CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells Matos, Anna L. L. Keller, Fabian Wegner, Tristan del Castillo, Carla Elizabeth Cadena Grill, David Kudruk, Sergej Spang, Anne Glorius, Frank Heuer, Andreas Gerke, Volker Commun Biol Article Cholesterol is an essential component of cellular membranes regulating the structural integrity and fluidity of biological bilayers and cellular processes such as signal transduction and membrane trafficking. However, tools to investigate the role and dynamics of cholesterol in live cells are still scarce and often show limited applicability. To address this, we previously developed a class of imidazolium-based cholesterol analogs, CHIMs. Here we confirm that CHIM membrane integration characteristics largely mimic those of cholesterol. Computational studies in simulated phospholipid bilayers and biophysical analyses of model membranes reveal that in biologically relevant systems CHIMs behave similarly to natural cholesterol. Importantly, the analogs can functionally replace cholesterol in membranes, can be readily labeled by click chemistry and follow trafficking pathways of cholesterol in live cells. Thus, CHIMs represent chemically versatile cholesterol analogs that can serve as a flexible toolbox to study cholesterol behavior and function in live cells and organisms. Nature Publishing Group UK 2021-06-11 /pmc/articles/PMC8196198/ /pubmed/34117357 http://dx.doi.org/10.1038/s42003-021-02252-5 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Matos, Anna L. L. Keller, Fabian Wegner, Tristan del Castillo, Carla Elizabeth Cadena Grill, David Kudruk, Sergej Spang, Anne Glorius, Frank Heuer, Andreas Gerke, Volker CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells |
title | CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells |
title_full | CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells |
title_fullStr | CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells |
title_full_unstemmed | CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells |
title_short | CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells |
title_sort | chims are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196198/ https://www.ncbi.nlm.nih.gov/pubmed/34117357 http://dx.doi.org/10.1038/s42003-021-02252-5 |
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