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Phase Transitions in Coarse-Grained Lipid Bilayers Containing Cholesterol by Molecular Dynamics Simulations
KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Biological Physics.
KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Biological Physics.
KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Biological Physics.ORCID iD: 0000-0002-7448-4664
2012 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 103, no 10, 2125-2133 p.Article in journal (Refereed) Published
Abstract [en]

Coarse-grained simulations of model membranes containing mixtures of phospholipid and cholesterol molecules at different concentrations and temperatures have been performed. A random mixing without tendencies for segregation or formation of domains was observed on spatial scales corresponding to a few thousand lipids and timescales up to several micro-seconds. The gel-to-liquid crystalline phase transition is successively weakened with increasing amounts of cholesterol without disappearing completely even at a concentration of cholesterol as high as 60%. The phase transition temperature increases slightly depending on the cholesterol concentration. The gel phase system undergoes a transition with increasing amounts of cholesterol from a solid-ordered phase into a liquid-ordered one. In the solid phase, the amplitude of the oscillations in the radial distribution function decays algebraically with a prefactor that goes to zero at the solid-liquid transition.

Place, publisher, year, edition, pages
2012. Vol. 103, no 10, 2125-2133 p.
Keyword [en]
particle mesh ewald, liquid water, model, tip4p/2005, spectra, range
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-102277DOI: 10.1016/j.bpj.2012.10.014ISI: 000311419000011Scopus ID: 2-s2.0-84869465857OAI: oai:DiVA.org:kth-102277DiVA: diva2:552045
Funder
Swedish Research CouncilSwedish e‐Science Research Center
Note

QC 20130107. Updated from accepted to published.

Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Molecular Dynamic Simulations of Biological Membranes
Open this publication in new window or tab >>Molecular Dynamic Simulations of Biological Membranes
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biological membranes mainly constituent lipid molecules along with some proteins and steroles. The properties of the pure lipid bilayers as well as in the presence of other constituents (in case of two or three component systems) are very important to be studied carefully to model these systems and compare them with the realistic systems. Molecular dynamic simulations provide a good opportunity to model such systems and to study them at microscopic level where experiments fail to do. In this thesis we study the structural and dynamic properties of the pure phospholipid bilayers and the phase behavior of phospholipid bilayers when other constituents are present in them. Material and structural properties like area per lipid and area compressibility of the phospholipids show a big scatter in experiments. These properties are studied for different system sizes and it was found that the increasing undulations in large systems effect these properties. A correction was applied to area per lipid and area compressibility using the Helfrich theory in Fourier space. Other structural properties like order of the lipid chains, electron density and radial distribution functions are calculated which give the structure of the lipid bilayer along the normal and in the lateral direction. These properties are compared to the X-ray and neutron scattering experiments after Fourier transform. Thermodynamic properties like heat capacity and heat of melting are also calculated from derivatives of energies available in molecular dynamics. Heat capacity on the other hand include quantum effect and are corrected for that by applying quantum correction using normal mode analysis for a simple as well as ambiguous system like water. Here it is done for SPC/E water model. The purpose of this study is to further apply the quantum corrections on macromolecules like lipids by using this technique. Furthermore the phase behavior of two component systems (phospholipids/cholesterol) is also studied. Phase transition in these systems is observed at different cholesterol concentrations as a function of temperature by looking at different quantities (as an order parameter) like the order of chains, area per molecule and partial specific area. Radial distribution functions are used to look at the in plane structure for different phases having a different lateral or positional order. Adding more cholesterol orders the lipid chains changing a liquid disordered system into a liquid ordered one and turning a solid ordered system into a liquid ordered one. Further more the free energy of domain formation is calculated to investigate the two phasecoexistence in binary systems. Free energy contains two terms. One is bulk freeenergy which was calculated by the chemical potential of cholesterol moleculein a homogeneous system which is favorable for segregation. Second is thefree energy of having an interface which is calculated from the line tension of the interface of two systems with different cholesterol concentration which in unfavorable for domain formation. The size of the domains calculated from these two contributions to the free energy gives the domains of a few nm in size. Though we could not find any such domains by directly looking at our simulations.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2012. vii, 78 p.
Series
Trita-FYS, ISSN 0280-316X ; 2012:68
Keyword
phospholipids, area compressibility, undulations, quantum corrections, cholesterol, phase transition, segregation
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-102268 (URN)978-91-7501-455-5 (ISBN)
Public defence
2012-09-24, Sal FA31, AlbaNova, Roslagstullsbacken 21, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

QC 20120913

Available from: 2012-09-13 Created: 2012-09-12 Last updated: 2012-09-13Bibliographically approved
2. Classical and Quantum Descriptions of Proteins, Lipids and Membranes
Open this publication in new window or tab >>Classical and Quantum Descriptions of Proteins, Lipids and Membranes
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis the properties of proteins and membranes are studied by molecular dynamics simulations. The subject is decomposed into parts addressing free energy calculations in proteins, mechanical inclusion models for lipid bilayers, phase transitions and structural correlations in lipid bilayers and atomistic lipid bilayer models. The work is based on results from large scale computer simulations, quantum mechanical and continuum models. Efficient statistical sampling and the coarseness of the models needed to describe the ordered and disordered states are of central concern.

Classical free energy calculations of zinc binding, in metalloproteins, require a quantum mechanical correction in order to obtain realistic binding energies. Classical electrostatic polarisation will influence the binding energy in a large region surrounding the ion and produce reasonable equilibrium structures in the bound state, when compared to experimental evidence.

The free energy for inserting a protein into a membrane is calculated with continuum theory. The free energy is assumed quadratic in the mismatch and depend on two elastic constants of the membrane. Under these circumstances, the free energy can then be written as a line tension multiplied by the circumference of the membrane inclusion. The inclusion model and coarse grained particle simulations of the membranes show that the thickness profile around the protein will be an exponentially damped oscillation.

Coarse-grained particle simulations of model membranes containing mixtures of phospholipid and cholesterol molecules at different conditions were performed. The gel-to-liquid crystalline phase transition is successively weakened with increasing amounts of cholesterol without disappearing even at a concentration of cholesterol as high as 60%.

A united atom parameterization of diacyl lipids was constructed. The aim was to construct a new force field that retains and improves the good agreement for the fluid phase and at the same time produces a gel phase at low temperatures, with properties coherent with experimental findings. The global bilayer tilt obtains an azimuthal value of 31and is aligned between lattice vectors in the bilayer plane. It is also shown that the model yield a correct heat of melting as well as heat capacities in the fluid and gel phase of DPPC.

 

Place, publisher, year, edition, pages
Stockholm, Sweden: KTH Royal Institute of Technology, 2014. xiv, 73 p.
Series
TRITA-FYS, ISSN 0280-316X ; 2014:55
Keyword
Quantum corrections, Coordination structure, Polarisation, Phase transitions, Kelvin differential equation, Line tension, Elastic membrane models, Molecular particle models, Zinc binding, Cholesterol and Phospholipids
National Category
Physical Sciences
Research subject
Biological Physics
Identifiers
urn:nbn:se:kth:diva-151396 (URN)978-91-7595-253-6 (ISBN)
Public defence
2014-10-03, Sal FA32, AlbaNova Universitetscentrum, Roslagstullsbacken 21, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council
Note

QC 20140919

Available from: 2014-09-19 Created: 2014-09-19 Last updated: 2014-10-07Bibliographically approved

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