Lithium fine tunes lipid membranes through phospholipid binding

Abstract Lithium is commonly prescribed for bipolar disorder due to its proven efficacy on patients. Despite this effectiveness, the molecular mechanisms underlying its action remain poorly understood, as it appears to influence numerous unrelated pathways. We propose that these diverse effects may...

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Main Authors: Louis Bunel, Vladimir Adrien, Jeff Coleman, Paul Heo, Frédéric Pincet
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-97828-0
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author Louis Bunel
Vladimir Adrien
Jeff Coleman
Paul Heo
Frédéric Pincet
author_facet Louis Bunel
Vladimir Adrien
Jeff Coleman
Paul Heo
Frédéric Pincet
author_sort Louis Bunel
collection DOAJ
description Abstract Lithium is commonly prescribed for bipolar disorder due to its proven efficacy on patients. Despite this effectiveness, the molecular mechanisms underlying its action remain poorly understood, as it appears to influence numerous unrelated pathways. We propose that these diverse effects may stem from a specific physicochemical event: the binding of lithium cations to phospholipid headgroups. In model membrane systems enabling direct observation of the lithium effects on lipid bilayers, we reveal that lithium binding stiffens the membrane, subsequently altering membrane protein activities. This mechanical impact of lithium links existing rationales, drawing a way to decipher the complex lithium effect in bipolar disorder (BD). To illustrate this global effect of lithium, we use the example of intracellular trafficking, a ubiquitous mechanism involving membrane reorganization in all organelles.
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spelling doaj-art-922b0bfa09714f3cbea57c17ea0731de2025-08-20T02:17:47ZengNature PortfolioScientific Reports2045-23222025-04-0115111210.1038/s41598-025-97828-0Lithium fine tunes lipid membranes through phospholipid bindingLouis Bunel0Vladimir Adrien1Jeff Coleman2Paul Heo3Frédéric Pincet4Laboratoire de Physique de l’École Normale Supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris CitéAP-HP, Department of Psychiatry, Avicenne Hospital, Paris Nord Sorbonne UniversitéNanobiology Institute, Yale UniversityINSERM, UMR-S 1266, Institut de Psychiatrie et Neurosciences de Paris, Université Paris CitéLaboratoire de Physique de l’École Normale Supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris CitéAbstract Lithium is commonly prescribed for bipolar disorder due to its proven efficacy on patients. Despite this effectiveness, the molecular mechanisms underlying its action remain poorly understood, as it appears to influence numerous unrelated pathways. We propose that these diverse effects may stem from a specific physicochemical event: the binding of lithium cations to phospholipid headgroups. In model membrane systems enabling direct observation of the lithium effects on lipid bilayers, we reveal that lithium binding stiffens the membrane, subsequently altering membrane protein activities. This mechanical impact of lithium links existing rationales, drawing a way to decipher the complex lithium effect in bipolar disorder (BD). To illustrate this global effect of lithium, we use the example of intracellular trafficking, a ubiquitous mechanism involving membrane reorganization in all organelles.https://doi.org/10.1038/s41598-025-97828-0
spellingShingle Louis Bunel
Vladimir Adrien
Jeff Coleman
Paul Heo
Frédéric Pincet
Lithium fine tunes lipid membranes through phospholipid binding
Scientific Reports
title Lithium fine tunes lipid membranes through phospholipid binding
title_full Lithium fine tunes lipid membranes through phospholipid binding
title_fullStr Lithium fine tunes lipid membranes through phospholipid binding
title_full_unstemmed Lithium fine tunes lipid membranes through phospholipid binding
title_short Lithium fine tunes lipid membranes through phospholipid binding
title_sort lithium fine tunes lipid membranes through phospholipid binding
url https://doi.org/10.1038/s41598-025-97828-0
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