Evidence for the Lack of a Specific Interaction between Cholesterol and Sphingomyelin

Abstract

The putative specific interaction and complex formation by sphingomyelin and cholesterol was investigated. Accordingly, low contents (1 mol % each) of fluorescently labeled derivatives of these lipids, namely 1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PyrPC), n-[10-(1-pyrenyl)decanoyl]sphingomyelin (PyrSM), and increasing concentrations of cholesterol (up to 5 mol %), were included in large unilamellar vesicles composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1,2-dinervonoyl-sn-glycero-3-phosphocholine (DNPC), and the excimer/monomer fluorescence emission ratio (I(e)/I(m)) was measured. In DNPC below the main phase transition, the addition of up to 5 mol % cholesterol reduced I(e)/I(m) significantly. Except for this, cholesterol had only a negligible effect in both matrices and for both probes. We then compared the efficiency of resonance energy transfer from PyrPC and PyrSM to 22-(n-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (NBDchol). An augmenting colocalization of the latter resonance energy transfer pair with temperature was observed in a DMPC matrix below the main phase transition. In contrast, compared to PyrSM the colocalization of PyrPC with NBDchol was more efficient in the longer DNPC matrix. These results could be confirmed using 5,6-dibromo-cholestan-3beta-ol as a collisional quencher for the pyrene-labeled lipids. The results indicate lack of a specific interaction between sphingomyelin and cholesterol, and further imply that hydrophobic mismatch between the lipid constituents could provide the driving force for the cosegregation of sphingomyelin and cholesterol in fluid phospholipid bilayers of thicknesses comparable to those found for biomembranes.

Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol

“…For example, both formulations account for the poor attack of cholesterol oxidase on mixed bilayers containing phospholipids with head groups that would shield sterols [5,57]. Furthermore, each mechanism could drive the condensation of phospholipid-sterol mixtures [58]. Both models serve the present argument by predicting an equivalence point in activity when phospholipids are titrated with sterols as well as the high activity of the excess free sterol monomers beyond this point.…”

“…In contrast, another molecular dynamics study concluded that the rough and smooth surfaces of the sterol were critical to how it organized the bilayer phospholipids laterally [47]. Finally, a lack of specificity in the interaction of cholesterol with sphingomyelin, considered to be its strongest membrane partner, has been inferred from detailed fluorescence studies [58]. Rather than specific associations, it has been suggested that congregation to minimize hydrophobic mismatch between the sterol and alkyl chains could be a driving force in their association [10,12].…”

Visualizing spatial lipid distribution in porcine lens by MALDI imaging high-resolution mass spectrometry

“…We found that the major phospholipid components were long chain phosphatidylcholines (PC) and SMs. The long chain PCs and SMs likely caused ordering of the lens fi ber membranes and allowed for more interactions between phospholipids and cholesterol ( 17 ).…”

Polydiacetylene Vesicles for Detecting Surfactants: Understanding the Driven Forces of Polydiacetylene-Surfactant Interaction

“…Approximately four times more CTAB was required to promote the same CR (40%) in the PDA/ CHO/SPH system compared to PDA vesicle. This behavior is explained by vesicle rigidity caused due to interaction between CHO and SPH molecules [32] and between them and with PDA via hydrogen bonding [33]; thus PDA/CHO/SPH were more thermodynamically stable structures [34] than pure PDA nanostructure.…”