Cholesterol-Induced Modifications in Lipid Bilayers: A Simulation Study

Chiu, See‐Wing; Jakobsson, Eric; Mashl, R. Jay; Scott, H. L.

doi:10.1016/s0006-3495(02)73949-0

Cited by 230 publications

(243 citation statements)

References 79 publications

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“…The area per molecule for a given configuration has been computed by dividing the size of the simulation box in the bilayer plane by the number of molecules in one monolayer. The area per molecule decreases monotonically with an increasing cholesterol concentration, in agreement with other simulations 15,62 and related experiments. 63 …”

Section: A Radial Distribution Functions and Areas Per Molecule Fromsupporting

confidence: 91%

Coarse-grained model for phospholipid/cholesterol bilayer

Murtola

Falck

Patra³

et al. 2004

The Journal of Chemical Physics

127

152

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We construct a coarse-grained (CG) model for dipalmitoylphosphatidylcholine (DPPC) / cholesterol bilayers and apply it to large-scale simulation studies of lipid membranes. Our CG model is a two-dimensional representation of the membrane, where the individual lipid and sterol molecules are described by point-like particles. The effective intermolecular interactions used in the model are systematically derived from detailed atomic-scale molecular dynamics simulations using the Inverse Monte Carlo technique, which guarantees that the radial distribution properties of the CG model are consistent with those given by the corresponding atomistic system. We find that the coarse-grained model for the DPPC / cholesterol bilayer is substantially more efficient than atomistic models, providing a speed-up of approximately eight orders of magnitude. The results are in favor of formation of cholesterol-rich and cholesterol-poor domains at intermediate cholesterol concentrations, in agreement with the experimental phase diagram of the system. We also explore the limits of the novel coarse-grained model, and discuss the general validity and applicability of the present approach.

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Section: A Radial Distribution Functions and Areas Per Molecule Fromsupporting

confidence: 91%

Coarse-grained model for phospholipid/cholesterol bilayer

Murtola

Falck

Patra³

et al. 2004

The Journal of Chemical Physics

127

152

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“…The corresponding areas per molecule are 0.65, 0.49, and 0.39 nm 2 , respectively, which are in good agreement with those obtained from MD simulations reported by other groups (Chiu et al, 2002;Saito and Shinoda, 2011). Additionally, the variances of A, , are 0.95, 0.54, and 0.23 nm 4 for the different cholesterol concentration bilayers, respectively.…”

Section: Estimation Of Line Tensionsupporting

confidence: 89%

Line tension of the pore edge in phospholipid/cholesterol bilayer from stretch molecular dynamics simulation

Shigematsu

Koshiyama

Wada

2015

JBSE

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The line tension of the pore in a phospholipid bilayer is important for pore-mediated molecular transport techniques. To understand the cholesterol effects on the line tension of the pore edge at the molecular level, we perform molecular dynamics simulations of phospholipid bilayers with a pore containing cholesterol in different concentrations (0, 20, and 40 mol%). The bilayer with a pore is prepared by using an equibiaxial stretching simulation. The stretched bilayer with a pore is subsequently compressed and the pore spontaneously closes when the applied areal strain of the bilayer is below a certain value. Using the pore closure areal strain and a free energy model of a stretched bilayer with a pore, the upper and lower limits of the line tensions for the bilayers containing cholesterol at 0, 20, and 40 mol% are estimated to be 17.0-48.2, 54.5-100, and 170-261 pN, respectively. The increasing tendency of the line tension qualitatively agrees with that observed experimentally. The pores in the cholesterol-containing bilayers are lined with several cholesterol molecules, which might increase the bending rigidity of the pore edge, and result in the higher line tension of the cholesterol-containing bilayer. The considerable dependency of the line tension on the bilayer compositions might be useful to explain the large variations of the transduction efficiency observed with sonoporation treatment.

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“…This behavior has been accurately modeled in terms of the thermodynamics of formation of condensed complexes [45]. Molecular dynamics simulations also support the concept of association of sterols with phospholipids [43,46,47]. Furthermore, such modeling suggests that these interactions can extend laterally beyond the complexes themselves, thereby ordering adjacent phospholipids over several molecular diameters [48].…”

Section: Stoichiometric Complexes Of Sterols and Phospholipidsmentioning

confidence: 67%

Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol

Lange

Steck

2008

Progress in Lipid Research

141

180

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We review evidence that sterols can form stoichiometric complexes with certain bilayer phospholipids, and sphingomyelin in particular. These complexes appear to be the basis for the formation of condensed and ordered liquid phases, (micro)domains and/or rafts in both artificial and biological membranes. The sterol content of a membrane can exceed the complexing capacity of its phospholipids. The excess, uncomplexed membrane sterol molecules have a relatively high escape tendency, also referred to as fugacity or chemical activity (and, here, simply activity). Cholesterol is also activated when certain membrane intercalating amphipaths displace it from the phospholipid complexes. Active cholesterol projects from the bilayer and is therefore highly susceptible to attack by cholesterol oxidase. Similarly, active cholesterol rapidly exits the plasma membrane to extracellular acceptors such as cyclodextrin and high-density lipoproteins. For the same reason, the pool of cholesterol in the ER (endoplasmic reticulum) increases sharply when cell surface cholesterol is incremented above the physiological set-point; i.e., equivalence with the complexing phospholipids. As a result, the escape tendency of the excess cholesterol not only returns the plasma membrane bilayer to its set point but also serves as a feedback signal to intracellular homeostatic elements to down-regulate cholesterol accretion.

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Cholesterol-Induced Modifications in Lipid Bilayers: A Simulation Study

Cited by 230 publications

References 79 publications

Coarse-grained model for phospholipid/cholesterol bilayer

Coarse-grained model for phospholipid/cholesterol bilayer

Line tension of the pore edge in phospholipid/cholesterol bilayer from stretch molecular dynamics simulation

Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol

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