Bicelles and Other Membrane Mimics: Comparison of Structure, Properties, and Dynamics from MD Simulations

Abstract

The increased interest in studying membrane proteins has led to the development of new membrane mimics such as bicelles and nanodiscs. However, only limited knowledge is available of how these membrane mimics are affected by embedded proteins and how well they mimic a lipid bilayer. Herein, we present molecular dynamics simulations to elucidate structural and dynamic properties of small bicelles and compare them to a large alignable bicelle, a small nanodisc, and a lipid bilayer. Properties such as lipid packing and properties related to embedding both an α-helical peptide and a transmembrane protein are investigated. The small bicelles are found to be very dynamic and mainly assume a prolate shape substantiating that small bicelles cannot be regarded as well-defined disclike structures. However, addition of a peptide results in an increased tendency to form disc-shaped bicelles. The small bicelles and the nanodiscs show increased peptide solvation and difference in peptide orientation compared to embedding in a bilayer. The large bicelle imitated a bilayer well with respect to both curvature and peptide solvation, although peripheral binding of short tailed lipids to the embedded proteins is observed, which could hinder ligand binding or multimer formation.

Nanodiscs in Membrane Biochemistry and Biophysics

“…176–178 Useful observations were made based on comparison of all-atom and CG simulations of Nanodiscs assembled with (Δ1–22) MSP1 and DMPC. 176 Both simulations revealed a high ordering of lipids in Nanodiscs and lower configuration entropy as compared to liposomes under the same conditions.…”

Artificial membranes for membrane protein purification, functionality and structure studies

“…They are formed by mixing membranes with a short chain lipid (or a detergent) and a long chain lipid [26][27][28][29]. The long chain phospholipid forms the membrane protein-containing bilayer, which is then stabilised by the short amphiphilic chain positioning at the rim of the bilayer [30]. The most popular choice so far is a combination of DHPC (dihexanoylphosphatidylcholine) (short) and DMPC (dimyristoylphosphatidylcholine) (long).…”

“…The most popular choice so far is a combination of DHPC (dihexanoylphosphatidylcholine) (short) and DMPC (dimyristoylphosphatidylcholine) (long). Bicelles adopt different conformations depending on the ratio of long to short lipids (the q-ratio), the temperature, pH and salt concentrations [30]. Simulations suggest that bicelles adopt a cigar-shaped structure that is converted into a disc-shaped structure when the integral membrane protein is added [30].…”

“…Bicelles adopt different conformations depending on the ratio of long to short lipids (the q-ratio), the temperature, pH and salt concentrations [30]. Simulations suggest that bicelles adopt a cigar-shaped structure that is converted into a disc-shaped structure when the integral membrane protein is added [30]. Protocols studying membrane proteins in bicelles have involved mixing bicelles with either purified proteins, when these are very stable, or detergent-solubilised proteins, but most bicelles are added as proteoliposome solutions.…”

“…Protocols studying membrane proteins in bicelles have involved mixing bicelles with either purified proteins, when these are very stable, or detergent-solubilised proteins, but most bicelles are added as proteoliposome solutions. Bicelles are thus native-like environments for membrane proteins [30].…”