Metabolic Precursor of Cholesterol Causes Formation of Chained Aggregates of Liquid-Ordered Domains
2016
Staneva, Galya | Osipenko, Denis S. | Galimzyanov, Timur R. | Pavlov, Konstantin V. | Akimov, Sergey A.
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.
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