Influence of Ganglioside GM1 Concentration on Lipid Clustering and Membrane Properties and Curvature.
Gangliosides are a class of glycosphingolipids (GSLs) with amphiphilic character that are found at the outer leaflet of the cell membranes, where their ability to organize into special domains makes them vital cell membrane components. However, a molecular understanding of GSL-rich membranes in terms of their clustered organization, stability, and dynamics is still elusive. To gain molecular insight into the organization and dynamics of GSL-rich membranes, we performed all-atom molecular-dynamics simulations of bicomponent ganglioside GM1 in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid bilayers with varying concentrations of GM1 (10%, 20%, and 30%). Overall, the simulations show very good agreement with available experimental data, including x-ray electron density profiles along the membrane normal, NMR carbohydrate proton-proton distances, and x-ray crystal structures. This validates the quality of our model systems for investigating GM1 clustering through an ordered-lipid-cluster analysis. The increase in GM1 concentration induces tighter lipid packing, driven mainly by inter-GM1 carbohydrate-carbohydrate interactions, leading to a greater preference for the positive curvature of GM1-containing membranes and larger cluster sizes of ordered-lipid clusters (with a composite of GM1 and POPC). These clusters tend to segregate and form a large percolated cluster at a 30% GM1 concentration at 293 K. At a higher temperature of 330 K, however, the segregation is not maintained.
Department of Biological Sciences and Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania.
Dhilon S
DS
Patel
Department of Biological Sciences and Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania.
Soohyung
S
Park
Department of Biological Sciences and Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania.
Emilia L
EL
Wu
Korean Institute of Science and Technology Information, Daejeon, Korea.
Min Sun
MS
Yeom
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden.
Göran
G
Widmalm
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland; Biophysics Program, University of Maryland, College Park, Maryland. Electronic address: jbklauda@umd.edu.
Jeffery B
JB
Klauda
Department of Biological Sciences and Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania. Electronic address: wonpil@lehigh.edu.
Wonpil
W
Im
D002236:Carbohydrate Conformation; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D013696:Temperature
D008051:Lipid Bilayers; D008563:Membrane Lipids; D009844:Oligosaccharides; D005677:G(M1) Ganglioside