Engineered Lipids That Cross-Link the Inner and Outer Leaflets of Lipid Bilayers
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文摘
The application of supported lipid bilayer systems as molecular sensors, diagnostic devices, and medicalimplants is limited by their lack of stability. In an effort to enhance the stability of supported lipid bilayers,three pairs of phosphatidylcholine lipids were designed to cross-link at the termini of their 2-position acylchain upon the formation of lipid bilayers. The cross-linked lipids span the lipid bilayer, resembling naturallyoccurring bolaamphiphiles that stabilize archaebacterial membranes against high temperatures. The threereactions investigated here include the acyl chain cross-linking between thiol and bromine groups, thioland acryloyl groups, and cyclopentadiene and acryloyl groups. All three reactive lipid pairs were foundto cross-link in liposomal membranes, as determined by thin-layer chromatography, ion-spray massspectrometry, and 1H NMR. The monolayer film properties of the reactive amphiphiles were characterizedby surface pressure-area isotherms and showed that stable monolayers formed at the air-water interfacewith limiting molecular areas comparable to that of pure saturated phosphatidylcholine lipids. Langmuir-Blodgett bilayers of dimyristoylphosphatidylcholine incorporating 15 mol % of the reactive thiol and acryloyllipids had diffusion coefficients comparable with pure dimyristoylphosphatidylcholine, while bilayers withmore than 25 mol % of the reactive lipids were immobile, suggesting that interleaflet cross-linking of thelipids inhibited membrane diffusion. Our results show that the reactive lipids can cross-link within a lipidbilayer and are suitable for assembling supported lipid bilayers using Langmuir-Blodgett deposition. Byusing terminally reactive amphiphiles to build up supported lipid bilayers with cross-linked leaflets,bolaamphiphiles can be incorporated into asymmetric solid supported membranes to increase their stabilityin biosensor and medical implant applications.

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