Lipid Bicelles in the Study of Biomembrane Characteristics

Abstract

Simulations of lipid membranes typically make use of periodic boundary conditions to mimic macroscopically sized membranes and allow for comparison to experiments performed e.g. on planar lipid membranes or on unilamellar lipid vesicles. However, the lateral periodicity partly suppresses membrane fluctuations or membrane remodeling, processes that are of particular importance in the study of asymmetric membranes–i.e. membranes with integral or associated proteins and/or asymmetric lipid compositions. Here, we devised a simple albeit powerful lipid bicelle model system that (i) displays similar structural, dynamical, and mechanical properties compared to infinite periodic lipid membrane systems and allows (ii) for the study of asymmetric lipid bilayer systems and (iii) the unperturbed formation of local spontaneous curvature induced by lipids or proteins in molecular dynamics simulations. In addition, the system is characterized by largely unbiased thermal fluctuations as opposed to standard bilayer systems. Application of the bicelle system for an asymmetric lipid composition resembling the plasma membrane reveals that the cholesterol density for a tension-free plasma membrane with a vanishing spontaneous curvature is larger by 28% within the extracellular leaflet compared to the cytosolic leaflet.

The intricate link between membrane lipid structure and composition and membrane structural properties in bacterial membranes

“…These encompass both lamellar and non-lamellar membrane models with a range of chemical compositions and intrinsic curvatures, including planar, rippled, local membrane protrusions/tubules, positively and negatively curved assemblies, micelles, bicelles, vesicles/liposomes, and various other shapes (up to and including full viral envelopes). 72,[80][81][82][83][84] In summary, the physical, structural and mechanical properties described above are all interrelated and inuenced by the lipid composition and extrinsic variables. They clearly paint a complex picture of membrane structure in terms of how the structural and physical properties are inuenced by changes in composition and extrinsic stress.…”

“…These encompass both lamellar and non-lamellar membrane models with a range of chemical compositions and intrinsic curvatures, including planar, rippled, local membrane protrusions/tubules, positively and negatively curved assemblies, micelles, bicelles, vesicles/liposomes, and various other shapes (up to and including full viral envelopes). 72,80–84…”

Effects of lipid saturation on bicelle to vesicle transition of a binary phospholipid mixture: a molecular dynamics simulation study

“…56,60 We calculated the mechanical properties of bicelles using independent lipid bilayer systems under periodic boundary conditions. So far, various methods have been developed for calculating k C with bilayer systems, 64 and recently, a method for calculating k C directly using bicelle systems 65 has been proposed. There are a few methods for obtaining % k C with MD simulations, 43,44 although it is difficult to validate them experimentally.…”

“…In addition, methods for structural analysis of bicelles are beginning to advance in MD studies. 65,67 Although their application to complex structural changes during vesicle formation may still be challenging, structural information at the molecular level can help understand vesiculation from bicelles.…”

Nonuniversal impact of cholesterol on membranes mobility, curvature sensing and elasticity

“…The latter is frequently equated with raft domains 6 . Experimental evidence for these sterol- and sphingolipid-enriched domains is still debated, as is the sterol distribution between the leaflets of plasma membranes dramatically differing between experimental studies 7 , 8 , with recent simulations hinting to a 28% increased cholesterol density within the extracellular leaflet 9 .…”