Modeling Lipid Particles

LDL

Low-density and high-density lipoproteins (LDL/HDL) transport cholesterol in the bloodstream, and play an important role in the development of atherosclerosis. Despite their importance to health, their structure is not known in detail. They consist of a mixture of components including phospholipids, triglycerides, cholesterol, and associated proteins. The Martini model has proven useful to study the structure and dynamics of these particles.

Studies were originally performed on a model spheroidal HDL particle [1], focusing on the overal shape of the particle and the role of the associated apoA-I protein; subsequent studies [2] involved a more realistic lipid distribution inside HDL. Most recently the much larger LDL particle was investigated using the Martini model [3] (see figure).

Other lipid based particles that have been simulated with Martini include a large variety of nanodiscs i.e., lipid bicelles stabilized by scaffolding proteins or DNA [8], or polymers [6], as well as liprotides [5]. In addition, the process of nanodroplet formation is being addressed with Martini [7]. To efficiently build such models, dedicated tools are available [4].

  • [1] A. Catte, J.C. Patterson, D. Bashtovyy, M.K. Jones, F. Gu, L. Li, A. Rampioni, D. Sengupta, T. Vuorela, P. Niemela, M. Karttunen, S.J. Marrink, I. Vattulainen, J.P. Segrest. Structure of spheroidal HDL particles revealed by combined atomistic and coarse grained simulations. Biophys. J., 94:2306-2319, 2008.
  • [2] T.A. Vuorela, A. Catte, P.S. Niemela, A. Hall, M.T. Hyvonen, S.J. Marrink, M. Karttunen, I. Vattulainen. Role of lipids in spheroidal high density lipoproteins. PLoS Comp. Biol., 6:e1000964, 2010.
  • [3] T. Murtola, T.A. Vuorela, M.T. Hyvonen, S.J. Marrink, M. Karttunen, I. Vattulainen. Low density lipoprotein: Structure, dynamics, and interactions of ApoB-100 with lipids. Soft Matter, 7:8135-8141, 2011.
  • [4] Y. Qi, H.I. Ingólfsson, X. Cheng, J. Lee, S.J. Marrink, W. Im. CHARMM-GUI Martini Maker for coarse-grained simulations with the Martini force field. JCTC, 11:4486–4494, 2015. abstract
  • [5] J.N. Pedersen, P.W.J.M. Frederix, J.S. Pedersen, S.J. Marrink, D. Otzen. Role of charge and hydrophobicity in liprotide formation: a molecular dynamics study with experimental constraints. ChemBioChem, 19:263–271, 2018. doi:10.1002/cbic.201700496
  • [6] M. Xue, L. Cheng, I. Faustino, W. Guo, S.J. Marrink. Molecular Mechanism of Lipid Nanodisk Formation by Styrene-Maleic Acid Copolymers. Biophys. J., 115:494-502, 2018. doi:10.1016/j.bpj.2018.06.018.
  • [7] X. Prasanna, V.T. Salo  et al. Seipin traps triacylglycerols to facilitate their nanoscale clustering in the endoplasmic reticulum membrane. PLoS Biol 19(1): e3000998, 2021. https://doi.org/10.1371/journal.pbio.3000998
  • [8]  V. Maingi, P.W.K. Rothemund. Properties of DNA- and Protein-Scaffolded Lipid Nanodiscs. ACS Nano 15:751–764, 2021. https://doi.org/10.1021/acsnano.0c07128