The doctoral dissertations of the former Helsinki University of Technology (TKK) and Aalto University Schools of Technology (CHEM, ELEC, ENG, SCI) published in electronic format are available in the electronic publications archive of Aalto University - Aaltodoc.

Computational Modelling of Lipid Bilayers with Sphingomyelin and Sterols

Perttu Niemelä

Dissertation for the degree of Doctor of Science in Technology to be presented with due permission of the Department of Engineering Physics and Mathematics for public examination and debate in Auditorium E at Helsinki University of Technology (Espoo, Finland) on the 20th of June, 2007, at 12 o'clock noon.

Overview in PDF format (ISBN 978-952-10-3713-9)   [2156 KB]
Dissertation is also available in print (ISBN 978-952-10-3712-2)


This thesis is based on atom-scale molecular dynamics simulations on lipid bilayers. The study concentrates on structural and dynamic properties of lipid bilayers, involving three lipid classes that are the main constituents of, for example, eukaryotic plasma membranes: phosphatidylcholines (PCs), sphingomyelins (SMs) and sterols. The discussion in the thesis starts from the simplest bilayers that are comprised of single lipid components, and gradually moves towards more complex systems, approaching a better description of biological membranes.

Studies on single-component bilayers concentrate on the properties of SM. In a comparison with a structurally similar PC, it is shown that the packing of SM in a bilayer is more compact and that the lipids are more ordered than in a PC bilayer. Additionally, unsaturation increases the fluidity of SM bilayer less than typically in PC bilayers. The above differences in the bilayer properties of SM and PC are explained by detailed analysis of the intra- and intermolecular hydrogen bonding in the SM bilayer. The results on the effects of chain length on SM bilayers are mainly involved with the bilayer thickness and the interdigitation of the longer chains through the bilayer centre.

The studies on sterols involves two parts. First, the molecular interactions of cholesterol (CHOL) with PC and SM lipids are characterised in detail. In particular, the aim is to reveal aspects of the SM-CHOL interaction, which has been proposed to be a key factor in the formation of lateral domains called lipid rafts in biological membranes. Second, the properties of bilayers with binary mixtures of PC and different sterols are discussed. It is shown that the acyl chain order in the studied systems is correlated with the tilt of the sterol. Also, we find that CHOL is superior among the studied sterols in ordering the acyl chains.

The studies on lipid raft bilayers involve three component mixtures of PC, SM, and CHOL. Large-scale simulations of two types of lipid environments are compared: raft-like membranes, which are high in SM and CHOL concentration, and non-raft membranes, which comprise of mostly PC. The results reveal that the raft-like membranes are much more rigid, ordered and packed, but also characterised by slower dynamics of the lipids, when compared to the non-raft environment. In the discussion, we show that the different properties of the two membrane environments may have significant implications on the functioning and partitioning of membrane proteins. In particular, the observed differences in the lateral pressure profiles are suggested to alter the open-state probability of an ion channel MscL.

This thesis consists of an overview and of the following 5 publications:

  1. Niemelä, P., Hyvönen, M. T., and Vattulainen, I., Structure and Dynamics of Sphingomyelin Bilayer: Insight Gained Through Systematic Comparison to Phosphatidylcholine, Biophysical Journal 87, 2976-2989 (2004). © 2004 Biophysical Society. By permission.
  2. Niemelä, P., Hyvönen, M. T., and Vattulainen, I., Influence of Chain Length and Unsaturation on Sphingomyelin Bilayers, Biophysical Journal 90, 851-863 (2006). © 2006 Biophysical Society. By permission.
  3. Aittoniemi, J., Róg, T., Niemelä, P., Pasenkiewicz-Gierula, M., Karttunen, M., and Vattulainen, I., Tilt: Major Factor in Sterols' Ordering Capability in Membranes, The Journal of Physical Chemistry B 110, 25562-25564 (2006).
  4. Aittoniemi, J., Niemelä, P. S., Hyvönen, M. T., Karttunen, M., and Vattulainen, I., Insight into the Putative Specific Interactions between Cholesterol, Sphingomyelin, and Palmitoyl-Oleoyl Phosphatidylcholine, Biophysical Journal 92, 1125-1137 (2007). © 2007 Biophysical Society. By permission.
  5. Niemelä, P. S., Ollila, S., Hyvönen, M. T., Karttunen, M., and Vattulainen, I., Assessing the Nature of Lipid Raft Membranes, PLoS Computational Biology 3, e34 (2007). © 2007 by authors.

Keywords: molecular dynamics, lipid rafts, cholesterol, sphingolipids

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© 2007 Helsinki University of Technology

Last update 2011-05-26