Covalent Solvatochromic Membrane Probe for Sensing Lipid Surrounding of Proteins
- 1University of Strasbourg
Abstract
Plasma membranes (PM) have been traditionally studied by fluorescent probes by either labelling lipid or protein parts. Based on our MemGraft concept, we report a fluorescent probe based on solvatochromic dye Nile Red (MemGraft-NR) for sensing lipid organization in the immediate surrounding of proteins, i.e. at the protein-lipid interface. Two sequentially attached MemGraft scaffolds are required to ensure robust grafting of Nile Red to PM. In contrast to classical lipid-bound membrane probes, MemGraft-NR exhibits high resistance to the presence of serum and fixation with permeabilization. Two-color confocal imaging of MemGraft-NR in live cells reveals higher polarity at the protein-lipid interface compared to lipid-bound probe NR12A. Surprisingly, MemGraft-NR displays higher sensitivity to variation of cholesterol content in PM compared to NR12A, suggesting that protein-lipid interface is particularly impacted by changes in the lipid composition. MemGraft-NR also enabled in situ monitoring of lipid exchange and permeabilization of PM, something impossible for classical solvatochromic PM probes. Unexpectedly, MemGraft-NR reveals a dramatic decrease in the local polarity in early endosomes, suggesting that endosomal negative curvature provides strong impact on organization of the protein-lipid interface. The developed probe opens a new way to study biological membranes by sensing lipid surrounding of membrane proteins.
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BibTeX
@misc{visser2026covalent,
title = {{Covalent Solvatochromic Membrane Probe for Sensing Lipid Surrounding of Proteins}},
author = {M. Visser and T. Loo Chin Moy and R. Pelletier and A. S. Klymchenko},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.03.756383},
url = {https://www.biorxiv.org/content/10.64898/2026.10.03.756383v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Covalent Solvatochromic Membrane Probe for Sensing Lipid Surrounding of Proteins
AU - M. Visser
AU - T. Loo Chin Moy
AU - R. Pelletier
AU - A. S. Klymchenko
PY - 2026
DA - 2026/10/03
PB - bioRxiv
DO - 10.64898/2026.10.03.756383
UR - https://www.biorxiv.org/content/10.64898/2026.10.03.756383v1
AB - Plasma membranes (PM) have been traditionally studied by fluorescent probes by either labelling lipid or protein parts. Based on our MemGraft concept, we report a fluorescent probe based on solvatochromic dye Nile Red (MemGraft-NR) for sensing lipid organization in the immediate surrounding of proteins, i.e. at the protein-lipid interface. Two sequentially attached MemGraft scaffolds are required to ensure robust grafting of Nile Red to PM. In contrast to classical lipid-bound membrane probes, MemGraft-NR exhibits high resistance to the presence of serum and fixation with permeabilization. Two-color confocal imaging of MemGraft-NR in live cells reveals higher polarity at the protein-lipid interface compared to lipid-bound probe NR12A. Surprisingly, MemGraft-NR displays higher sensitivity to variation of cholesterol content in PM compared to NR12A, suggesting that protein-lipid interface is particularly impacted by changes in the lipid composition. MemGraft-NR also enabled in situ monitoring of lipid exchange and permeabilization of PM, something impossible for classical solvatochromic PM probes. Unexpectedly, MemGraft-NR reveals a dramatic decrease in the local polarity in early endosomes, suggesting that endosomal negative curvature provides strong impact on organization of the protein-lipid interface. The developed probe opens a new way to study biological membranes by sensing lipid surrounding of membrane proteins.
ER -