Molecular Modeling of Cardiolipin
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Biological membranes are assembled from many different lipids. Our understanding of membrane function and morphology is dependent on linking the properties of the lipids to the properties of the membranes. In the inner mitochondrial membrane, one of the main lipids is cardiolipin, which is involved in the formation of high curvature tubular regions. In this thesis a series of molecular models of cardiolipin is presented, with the aim of providing a bottom-up understanding for its influence on model and biological membranes. The models allow detailed control over the headgroup charge and the chain volumes, which experimentally have shown to be important for the packing, mechanical, and electrostatic properties of membranes.To achieve these aims, three levels of detail were used: i) quantum chemical calculations for the cardiolipin headgroup, ii) atomistic united atom molecular dynamics simulations for cardiolipin and phosphatidylcholine lipid mixtures, and iii) coarse grained molecular dynamics simulations for larger lipid systems, including phase transitions between the micellar, lamellar, and inverse hexagonal phases, as well as mixtures of cardiolipin with zwitterionic lipids. These models are presented in the context of various experiments on cardiolipin systems done by others, and some basic theory of electrostatics and mechanics of membranes are discussed.The simple coarse grained model gave lipid phase preferences in agreement with experimental data. Relatively small amounts of partially neutralized cardiolipin molecules introduced mechanical instability in phosphatidylcholine bilayers, and showed some evidence of domain formation due to curvature frustration. The small effective headgroup volume of cardiolipin induced order in the hydrocarbon chains, partly due to strong sodium ion binding. Different types of intramolecular hydrogen bond networks in cardiolipin were described, and proton transfer between the phosphate groups within a cardiolipin molecule was estimated to have a 4-5 kcal/mol barrier. Such transfer might play a role in the surface conduction of protons at the inner mitochondrial membrane.
Place, publisher, year, edition, pages
Stockholm: Department of Materials and Environmental Chemistry (MMK), Stockholm University , 2010. , 97 p.
Research subject Physical Chemistry
IdentifiersURN: urn:nbn:se:su:diva-37613ISBN: 978-91-7447-024-6OAI: oai:DiVA.org:su-37613DiVA: diva2:304024
2010-04-16, Magnelisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:00 (English)
Pastor, Richard W., PhD
Maliniak, Arnold, Professor
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Submitted.2010-03-252010-03-162010-03-17Bibliographically approved
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