Dynamic properties of isotropic DMPC/DHPC bicelles: Insights from solution NMR and MD simulations

Bicelles, an artificial disk-shaped lipid bilayer, are commonly used for the structural and functional characterization of membrane-bound proteins in an environment similar to that in intracellular membranes. Because the dynamics of the lipids that constitute bicelles exert a significant impact on the structure and function of the inserted proteins, we investigated the mobility of lipid molecules in bicelles composed of DMPC (14:0 PC) and DHPC (06:0 PC) using solution NMR and MD calculations. ¹³C R₁ relaxation experiments for the acyl groups demonstrated that increasing bicelle sizes limit the rotational diffusion of acyl chain H-C bonds in DMPC. Such a limited local motion around H-C bonds was also predicted in the MD simulations of DMPC bilayers with decreased area per lipid, indicating that the limited mobility of the hydrophobic core in larger bicelles is due to the tighter lipid packing. The downfield shifts of the ¹³C NMR signals of the acyl groups supported the restricted mobility, corresponding to the conformational changes of the acyl chains from the flexible gauche rotamers to the less mobile trans rotamers with increase in bicelle size. These data suggest that larger bicelles pack lipids more densely, leading to increased trans conformation of the acyl chains and, consequently, less lipid motility, which can dynamically modulate the structure and function of membrane-bound proteins inserted into the bicelles.