Influence of the Long-Chain/Short-Chain Amphiphile Ratio on Lateral Diffusion of PEG-Lipid in Magnetically Aligned Lipid Bilayers as Measured via Pulsed-Field-Gradient NMR

Lateral diffusion measurements of polyethylene glycol(PEG)-lipid incorporated into magnetically aligned lipid bilayers, composed of dimyristoyl phosphatidylcholine (DMPC) plus dihexanoyl phosphatidylcholine (DHPC) plus 1 mol % (relative to DMPC) dimyristoyl phosphatidylethanolamine-n-[methoxy(polyethylene glycol)-2000] (DMPE-PEG 2000), were performed using stimulated-echo pulsed-field-gradient proton (1H) nuclear magnetic resonance spectroscopy. The DMPE-PEG 2000 (1 mol %, 35°C) lateral diffusion coefficient D varied directly with the mole fraction of DMPC, XDMPC = q/(1+q) where q = DMPC/DHPC molar ratio, decreasing progressively from D = 1.65 × 10−11 m2 s−1 at q ≈ 4.7 to D = 0.65 × 10−11 m2 s−1 at q ≈ 2.5. Possible sources of this dependence, including orientational disorder, obstruction, and PEG-lipid sequestration, were simulated using, respectively, a diffusion-in-a-cone model, percolation theory, and a two-phase PEG distribution model. Orientational disorder alone was not capable of reproducing the observations, but in combination with either obstruction or PEG-lipid two-phase distribution models did so satisfactorily. A combination of all three models yielded the most reasonable fit to the observed dependence of lateral diffusion on q. These same effects would be expected to influence lateral diffusion of any bilayer-associating species in such systems.