Assessing the Nature of Lipid Raft Membranes

Role of sterol type on lateral pressure profiles of lipid membranes affecting membrane protein functionality: Comparison between cholesterol, desmosterol, 7-dehydrocholesterol and ketosterol

“…More importantly, though, if we consider the work needed to be done against the lateral pressure in order to reshape the cavity of a protein in the bilayer, we find that it varies by several k B T, depending on the sterol type. Further studies have shown that in lipid raft-like bilayer compositions the same quantity is about 11k B T (Niemelä et al, 2007). While these results are suggestive and concern only the mechanosensitive channel MScL studied here as an example, they demonstrate that the contribution due to the lateral pressure profile may correspond to a significant fraction of the free energy cost between the open and closed states of a membrane protein.…”

“…In unsaturated bilayers the differences between the different sterol types are smaller. For comparison, significantly larger values have been found recently in simulations of a lipid raft-like bilayer (Niemelä et al, 2007) for an equimolar mixture of cholesterol, sphingomyelin, and POPC. For that system a similar analysis yielded DW % 11 k B T. Using a simplified lattice model, the theoretical study by Cantor, 1999a) resulted in values which were of the same order of magnitude.…”

“…It is likely, though, that the lipid composition surrounding the protein does matter considerably. This is particularly evident from (Niemelä et al, 2007) and Table 2, which highlight the difference between varying lipid compositions in bilayer systems.…”

“…Summarizing, we find that the seemingly minor structural differences between the sterols are manifested as observable differences in DW. This is most evident in saturated bilayers and supported by significant effects in very compact raft-like bilayers (Niemelä et al, 2007).…”

Formation and regulation of lipid microdomains in cell membranes: Theory, modeling, and speculation

“…Second, the spatially-extended nature of the membrane ''patchiness" together with dynamic membrane processes, due to both thermodynamic fluctuations and non-equilibrium cellular events (such as endo-and exocytosis), make direct atomistic simulations of membrane processes of rather limited value due to stringent restrictions on accessible length and time scales. To date, the most extensive simulations with atomistic detail relevant for raft studies have been carried out by Niemelä et al [25] and Risselada and Marrink [26]. The former study focused on the structural properties of the l o and l d phases in a ternary lipid system via molecular dynamics simulations extending up to 100 ns, while the latter employed a coarse-grained molecular model to elucidate the early-time formation kinetics of phase separated lipid domains in a ternary lipid system.…”