title: Metabolic Precursor of Cholesterol Causes Formation of Chained Aggregates of Liquid-Ordered Domains.
abstract: 7-Dehydrocholesterol, an immediate metabolic predecessor of cholesterol, can accumulate in tissues due to some metabolic abnormalities, causing an array of symptoms known as Smith-Lemli-Opitz syndrome. Enrichment of cellular membranes with 7-dehydrocholesterol interferes with normal cell-signaling processes, which involve interaction between rafts and formation of the so-called signaling platforms. In model membranes, cholesterol-based ordered domains usually merge upon contact. According to our experimental data, ordered domains in the model systems where cholesterol is substituted for 7-dehydrocholesterol never merge on the time scale of the experiment, but clusterize into necklace-like aggregates. We attribute such different dynamical behavior to altered properties of the domain boundary. In the framework of thickness mismatch model, we analyzed changes of interaction energy profiles of two approaching domains caused by substitution of cholesterol by 7-dehydrocholesterol. The energy barrier for domain merger is shown to increase notably, with simultaneous appearance of another distinct local energy minimum. Such energy profile is in perfect qualitative agreement with the experimental observations. The observed change of domain dynamics can impair proper interaction between cellular rafts underlying pathologies associated with deviations in cholesterol metabolism.
authors.affiliation: Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences , 21 Academic G. Bonchev Str., Sofia 1113, Bulgaria.
authors.forename: Galya
authors.initials: G
authors.lastname: Staneva
authors.affiliation: A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences , 31/4 Leninskiy prospekt, Moscow 119071, Russia.
authors.forename: Denis S
authors.initials: DS
authors.lastname: Osipenko
authors.affiliation: A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences , 31/4 Leninskiy prospekt, Moscow 119071, Russia.|National University of Science and Technology "MISiS" , 4 Leninskiy prospect, Moscow 119049, Russia.
authors.forename: Timur R
authors.initials: TR
authors.lastname: Galimzyanov
authors.affiliation: A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences , 31/4 Leninskiy prospekt, Moscow 119071, Russia.
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Pavlov
authors.affiliation: A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences , 31/4 Leninskiy prospekt, Moscow 119071, Russia.|National University of Science and Technology "MISiS" , 4 Leninskiy prospect, Moscow 119049, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Akimov
mesh_terms: D002784:Cholesterol / Q000737:chemistry; D003684:Dehydrocholesterols / Q000737:chemistry*; D004548:Elasticity; D021962:Membrane Microdomains / Q000737:chemistry*; D008956:Models, Chemical; D010713:Phosphatidylcholines / Q000737:chemistry; D013109:Sphingomyelins / Q000737:chemistry; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D003684:Dehydrocholesterols; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D053835:Unilamellar Liposomes; D002784:Cholesterol; C016705:7-dehydrocholesterol