Molecular Simulation of the DMPC-Cholesterol Phase Diagram

Abstract

In this paper, we present a coarse-grained model of a hydrated saturated phospholipid bilayer (dimyristoylphosphatidylcholine, DMPC) containing cholesterol that we study using a hybrid dissipative particle dynamics-Monte Carlo method. This approach allows us to reach the time and length scales necessary to study structural and mechanical properties of the bilayer at various temperatures and cholesterol concentrations. The properties studied are the area per lipid, condensation, bilayer thickness, tail order parameters, bending modulus, and area compressibility. Our model quantitatively reproduces most of the experimental effects of cholesterol on these properties and reproduces the main features of the experimental phase and structure diagrams. We also present all-atom simulation results of the system and use these results to further validate the structure of our coarse-grained bilayer. On the basis of the changes in structural properties, we propose a temperature-composition structure diagram, which we compare with the experimental phase and structure diagrams. Attention is paid to the reliability and interpretation of the model and simulation method and of the different experimental techniques. The lateral organization of cholesterol in the bilayer is discussed.

Understanding the Phase Behavior of Coarse-Grained Model Lipid Bilayers through Computational Calorimetry

“…Connecting h 3 (t 4 ) 2 with DMPC as done in ref 15 and assigning three methyl(ene) groups per additional bead, this set of lipids corresponds to simulating tail lengths ranging from 14 carbons per saturated tail up to 23 carbons per tail. We shall employ the standard notation Cn C :0 with the first number indicating the number of carbons in the fatty acid chain and the second number indicating zero double bonds.…”

“…31,32 For the various computational models, we compare structural quantities of the bilayer, similar to examinations previously published for the DPD model of saturated lipids and cholesterol. 14,15 The liquidÀgel transition has also been examined using the MARTINI model by considering the local coordination of beads within the lipid tails, monitoring the extent of lateral 6-fold coordination of tail beads as a gauge of the existence of the gel phase during instantaneous quenches of the bilayer across transition boundaries. 21 Here we instead consider quasistatic cooling and heating of the MARTINI bilayers, examining more aggregate structural quantities such as area and order parameters, similar to the previous DPD studies.…”

“…Previous studies 11,15,21 have characterized these phase transitions using a combination of visual inspection and the inflection point for structural properties as a function of temperature. We seek to characterize these transitions by a thermodynamically well-defined quantity: the enthalpy change associated with these phase transformations.…”

Lipid mediated packing of transmembrane helices – a dissipative particle dynamics study

“…For a detailed description of the simulation technique and parameters we refer to previously published work. 31 Energy and length are measured in reduced units:…”

“…27,28 Coarse-grained (CG) simulations, in which sets of atoms are grouped together to one bead, allow faster computation and have been used to probe biologically relevant time and length scales. 16,23,29,30 These models were shown to be successful in predicting bulk material properties 31 as well as in describing molecular level phenomena. [32][33][34] In this paper we explore the effect of hydrophobic mismatch on the cross-angle distribution of simulated TM helices.…”