Regimes of Complex Lipid Bilayer Phases Induced by Cholesterol Concentration in MD Simulation.

Abstract:

:Cholesterol is essential to the formation of phase-separated lipid domains in membranes. Lipid domains can exist in different thermodynamic phases depending on the molecular composition and play significant roles in determining structure and function of membrane proteins. We investigate the role of cholesterol in the structure and dynamics of ternary lipid mixtures displaying phase separation using molecular dynamics simulations, employing a physiologically relevant span of cholesterol concentration. We find that cholesterol can induce formation of three regimes of phase behavior: 1) miscible liquid-disordered bulk, 2) phase-separated, domain-registered coexistence of liquid-disordered and liquid-ordered domains, and 3) phase-separated, domain-antiregistered coexistence of liquid-disordered and newly identified nanoscopic gel domains composed of cholesterol threads we name "cholesterolic gel" domains. These findings are validated and discussed in the context of current experimental knowledge, models of cholesterol spatial distributions, and models of ternary lipid-mixture phase separation.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Pantelopulos GA,Straub JE

doi

10.1016/j.bpj.2018.10.011

subject

Has Abstract

pub_date

2018-12-04 00:00:00

pages

2167-2178

issue

11

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(18)31158-5

journal_volume

115

pub_type

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