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Singular Interaction between an Antimetastatic Agent and the Lipid Bilayer: The Ohmline Case

dc.contributor.authorHERRERA, F. E.
dc.contributor.authorSEVRAIN, C. M.
dc.contributor.authorJAFFRES, P. A.
dc.contributor.authorCOUTHON, H.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorGRELARD, Axelle
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorDUFOURC, Erick J.
dc.contributor.authorCHANTOME, A.
dc.contributor.authorPOTIER-CARTEREAU, M.
dc.contributor.authorVANDIER, C.
dc.contributor.authorBOUCHET, A. M.
dc.date.accessioned2020-07-09T14:16:51Z
dc.date.available2020-07-09T14:16:51Z
dc.date.issued2017-10
dc.identifier.issn2470-1343
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10314
dc.description.abstractEnSK3 channels are abnormaly expressed in metastatic cells, and Ohmline (OHM), an ether lipid, has been shown to reduce the activity of SK3 channels and the migration capacity of cancer cells. OHM incorporation into the plasma membrane is proposed to dissociate the protein complex formed between SK3 and Orai1, a potassium and a calcium channel, respectively, and would lead to a modification in the lipid environment of both the proteins. Here, we report the synthesis of deuterated OHM that affords the determination, through solid-state NMR, of its entire partitioning into membranes mimicking the SK3 environment. Use of deuterated lipids affords the demonstration of an OHM-induced membrane disordering, which is dose-dependent and increases with increasing amounts of cholesterol (CHOL). Molecular dynamics simulations comfort the disordering action and show that OHM interacts with the carbonyl and phosphate groups of stearoylphosphatidylcholine and sphingomyelin and to a minor extent with CHOL. OHM is thus proposed to remove the CHOL OH moieties away from their main binding sites, forcing a new rearrangement with other lipid groups. Such an interaction takes its origin at the lipid-water interface, but it propagates toward the entire lipid molecules and leads to a cooperative destabilization of the lipid acyl chains, that is, membrane disordering. The consequences of this reorganization of the lipid phases are discussed in the context of the OHM-induced inhibition of SK3 channels.
dc.title.enSingular Interaction between an Antimetastatic Agent and the Lipid Bilayer: The Ohmline Case
dc.typeArticle de revue
dc.identifier.doi10.1021/acsomega.7b00936
dc.subject.halChimie/Matériaux
bordeaux.journalAcs Omega
bordeaux.page6361-6370
bordeaux.volume2
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248*
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN, UMR 5248)
bordeaux.issue10
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
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