Critical size dependence of domain formation observed in coarse-grained simulations of bilayers composed of ternary lipid mixtures

Abstract

Model cellular membranes are known to form micro- and macroscale lipid domains dependent on molecular composition. The formation of macroscopic lipid domains by lipid mixtures has been the subject of many simulation investigations. We present a critical study of system size impact on lipid domain phase separation into liquid-ordered and liquid-disordered macroscale domains in ternary lipid mixtures. In the popular di-C16:0 PC:di-C18:2 PC:cholesterol at 35:35:30 ratio mixture, we find systems with a minimum of 1480 lipids to be necessary for the formation of macroscopic phase separated domains and systems of 10 000 lipids to achieve structurally converged conformations similar to the thermodynamic limit. To understand these results and predict the behavior of any mixture forming two phases, we develop and investigate an analytical Flory-Huggins model which is recursively validated using simulation and experimental data. We find that micro- and macroscale domains can coexist in ternary mixtures. Additionally, we analyze the distributions of specific lipid-lipid interactions in each phase, characterizing domain structures proposed based on past experimental studies. These findings offer guidance in selecting appropriate system sizes for the study of phase separations and provide new insights into the nature of domain structure for a popular ternary lipid mixture.

Twisting and tilting of a mechanosensitive molecular probe detects order in membranes

“…Due to the slow diffusion of lipids and the microsecond timescale required to form lipid domains, most of MD studies involving simulations of lipid nanodomains employ coarsegrained models, 20,[86][87][88][89][90][91] although few studies using all-atom simulations can be found in the literature. 78,79,[92][93][94][95] Here, we retain the atomic-level resolution of Flipper-TR as its working mechanism may not be accurately represented by a coarsegrained model.…”

The aggregation of striped nanoparticles in mixed phospholipid bilayers

“…An equilibrium average of one represents a perfect hexagonal packing and zero represents disordered packing. The phospholipid beads C2A/C2B and D2A/D2B (where A and B labels represent the two hydrophobic tails) in the phospholipid tail groups were used as points of reference with respect to the arbitrary vector 57 . All visualisations and analysis were implemented using a combination of VMD 58 , APLVoro 59 and MD-Analysis 60 , along with in-house scripts.…”

Characterization of dynamics and mechanism in the self-assembly of AOT reverse micelles

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