Title
The Delicate Dance of Cholesterol and Biological Water in Membrane Heterogeneity and Fusion
Authors
[ 1 ] Instytut Fizyki, Wydział Inżynierii Materiałowej i Fizyki Technicznej, Politechnika Poznańska | [ 2 ] Wydział Inżynierii Materiałowej i Fizyki Technicznej, Politechnika Poznańska | [ P ] employee | [ SzD ] doctoral school student
Scientific discipline (Law 2.0)
Year of publication
2025
Published in
Article type
abstract
Publication language
english
Abstract
EN Cholesterol-rich lipid rafts facilitate membrane fusion, a process central to fertilization, neurotransmission, and viral entry. However, the molecular interplay between cholesterol, phospholipids, and water in regulating this process remains poorly understood. Using confocal fluorescence microscopy, environment-sensitive probes, and MD simulations, we revealed that membrane dehydration—mimicking fusion relevant conditions—triggers cholesterol release from raft-like domains into the surrounding fluid phase. This likely provides a regulatory mechanism to prevent excessive fluidity fluctuations that could destabilize the cell membrane. Since membrane-bound water molecules play a key role in fusion dynamics, we employed heterodyne-detected vibrational sum-frequency generation spectroscopy to examine how cholesterol influences water alignment. We provide the first direct evidence that cholesterol, by modulating inter-lipid interactions, alters the orientation of the nanoscopic water layer that hydrates the membrane. This effect varies significantly between raft and non-raft environments. Overall, our findings suggest that cholesterol levels may be actively regulated at fusion sites to control membrane fusion events.
Pages (from - to)
137 - 137
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