A Multifunctional Probe for Visualization of the Nanoscale Distribution of Cholesterol in Cells by Expansion Microscopy

ABSTRACT Unraveling the nanoscale distribution of small molecules in cells is of central importance for the understanding of cellular functions and the development of drugs. However, particularly the visualization of lipids such as cholesterol—a central compound of cell membranes—with high spatial r...

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Main Authors: Gang Wen, Dominic A. Helmerich, Lisa Behringer‐Pließ, Markus Sauer
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Aggregate
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Online Access:https://doi.org/10.1002/agt2.70104
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author Gang Wen
Dominic A. Helmerich
Lisa Behringer‐Pließ
Markus Sauer
author_facet Gang Wen
Dominic A. Helmerich
Lisa Behringer‐Pließ
Markus Sauer
author_sort Gang Wen
collection DOAJ
description ABSTRACT Unraveling the nanoscale distribution of small molecules in cells is of central importance for the understanding of cellular functions and the development of drugs. However, particularly the visualization of lipids such as cholesterol—a central compound of cell membranes—with high spatial resolution remains challenging because they cannot be efficiently immobilized for super‐resolution microscopy investigations. Here we developed an azido‐ and amino‐modified cholesterol probe that can be efficiently fixed and labeled with fluorophores by click chemistry. In combination with expansion microscopy, its cellular localization and interaction with other cellular proteins can be precisely determined in fixed cells at varying time points after addition. Our approach allows us to detect the endocytic pathway of cholesterol with unprecedented spatial resolution and shows that cholesterol is efficiently ingested in endocytic vesicles and accumulates as cholesterol aggregates with an average size of ∼37 nm in late endosomes and lysosomes, respectively.
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issn 2692-4560
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publishDate 2025-08-01
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spelling doaj-art-5c51740da8f148a293f8e6b4bccc49002025-08-21T14:18:22ZengWileyAggregate2692-45602025-08-0168n/an/a10.1002/agt2.70104A Multifunctional Probe for Visualization of the Nanoscale Distribution of Cholesterol in Cells by Expansion MicroscopyGang Wen0Dominic A. Helmerich1Lisa Behringer‐Pließ2Markus Sauer3Department of Biotechnology and Biophysics Biocenter University of Würzburg Wurzburg GermanyDepartment of Biotechnology and Biophysics Biocenter University of Würzburg Wurzburg GermanyDepartment of Biotechnology and Biophysics Biocenter University of Würzburg Wurzburg GermanyDepartment of Biotechnology and Biophysics Biocenter University of Würzburg Wurzburg GermanyABSTRACT Unraveling the nanoscale distribution of small molecules in cells is of central importance for the understanding of cellular functions and the development of drugs. However, particularly the visualization of lipids such as cholesterol—a central compound of cell membranes—with high spatial resolution remains challenging because they cannot be efficiently immobilized for super‐resolution microscopy investigations. Here we developed an azido‐ and amino‐modified cholesterol probe that can be efficiently fixed and labeled with fluorophores by click chemistry. In combination with expansion microscopy, its cellular localization and interaction with other cellular proteins can be precisely determined in fixed cells at varying time points after addition. Our approach allows us to detect the endocytic pathway of cholesterol with unprecedented spatial resolution and shows that cholesterol is efficiently ingested in endocytic vesicles and accumulates as cholesterol aggregates with an average size of ∼37 nm in late endosomes and lysosomes, respectively.https://doi.org/10.1002/agt2.70104expansion microscopy | multifunctional cholesterol probes | super‐resolution | tracking
spellingShingle Gang Wen
Dominic A. Helmerich
Lisa Behringer‐Pließ
Markus Sauer
A Multifunctional Probe for Visualization of the Nanoscale Distribution of Cholesterol in Cells by Expansion Microscopy
Aggregate
expansion microscopy | multifunctional cholesterol probes | super‐resolution | tracking
title A Multifunctional Probe for Visualization of the Nanoscale Distribution of Cholesterol in Cells by Expansion Microscopy
title_full A Multifunctional Probe for Visualization of the Nanoscale Distribution of Cholesterol in Cells by Expansion Microscopy
title_fullStr A Multifunctional Probe for Visualization of the Nanoscale Distribution of Cholesterol in Cells by Expansion Microscopy
title_full_unstemmed A Multifunctional Probe for Visualization of the Nanoscale Distribution of Cholesterol in Cells by Expansion Microscopy
title_short A Multifunctional Probe for Visualization of the Nanoscale Distribution of Cholesterol in Cells by Expansion Microscopy
title_sort multifunctional probe for visualization of the nanoscale distribution of cholesterol in cells by expansion microscopy
topic expansion microscopy | multifunctional cholesterol probes | super‐resolution | tracking
url https://doi.org/10.1002/agt2.70104
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