title: Effect of neurosteroids on a model lipid bilayer including cholesterol: An Atomic Force Microscopy study.
abstract: Amphiphilic molecules which have a biological effect on specific membrane proteins, could also affect lipid bilayer properties possibly resulting in a modulation of the overall membrane behavior. In light of this consideration, it is important to study the possible effects of amphiphilic molecule of pharmacological interest on model systems which recapitulate some of the main properties of the biological plasma membranes. In this work we studied the effect of a neurosteroid, Allopregnanolone (3α,5α-tetrahydroprogesterone or Allo), on a model bilayer composed by the ternary lipid mixture DOPC/bSM/chol. We chose ternary mixtures which present, at room temperature, a phase coexistence of liquid ordered (Lo) and liquid disordered (Ld) domains and which reside near to a critical point. We found that Allo, which is able to strongly partition in the lipid bilayer, induces a marked increase in the bilayer area and modifies the relative proportion of the two phases favoring the Ld phase. We also found that the neurosteroid shifts the miscibility temperature to higher values in a way similarly to what happens when the cholesterol concentration is decreased. Interestingly, an isoform of Allo, isoAllopregnanolone (3β,5α-tetrahydroprogesterone or isoAllo), known to inhibit the effects of Allo on GABAA receptors, has an opposite effect on the bilayer properties.
authors.affiliation: Dipartimento di Scienze Fisiche, Matematiche e Informatiche, Via Campi 213/A, 41125 Modena, Italy; CNR - Istituto Nanoscienze, S3, Via Campi 213/A, 41125 Modena, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Sacchi
authors.affiliation: CNR - Istituto Nanoscienze, S3, Via Campi 213/A, 41125 Modena, Italy.
authors.forename: Daniel
authors.initials: D
authors.lastname: Balleza
authors.affiliation: Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Via Campi 287, Modena 287, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Vena
authors.affiliation: Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Via Campi 287, Modena 287, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Puia
authors.affiliation: CNR - Istituto di Biofisica, Via De Marini 6, 16149 Genova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Facci
authors.affiliation: Dipartimento di Scienze Fisiche, Matematiche e Informatiche, Via Campi 213/A, 41125 Modena, Italy; CNR - Istituto Nanoscienze, S3, Via Campi 213/A, 41125 Modena, Italy. Electronic address: andrea.alessandrini@unimore.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Alessandrini
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D007536:Isomerism; D008051:Lipid Bilayers; D018625:Microscopy, Atomic Force; D018377:Neurotransmitter Agents / Q000737:chemistry* / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000737:chemistry*; D011280:Pregnanolone / Q000737:chemistry* / Q000494:pharmacology; D013109:Sphingomyelins / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry* / Q000494:pharmacology; D044366:Transition Temperature
chemical_list: D008051:Lipid Bilayers; D018377:Neurotransmitter Agents; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D013501:Surface-Active Agents; D002784:Cholesterol; D011280:Pregnanolone; C017251:1,2-oleoylphosphatidylcholine
keywords: Allopregnanolone; Atomic Force Microscopy; Critical fluctuation; Liquid ordered domain; Neurosteroid