title: Folding of lipid monolayers containing lung surfactant proteins SP-B(1-25) and SP-C studied via coarse-grained molecular dynamics simulations.
abstract: To explore the role of lung surfactant proteins SP-B and SP-C in storing and redelivering lipid from lipid monolayers during the compression and re-expansion occurring in lungs during breathing, we simulate the folding of lipid monolayers with and without these proteins. We utilize the MARTINI coarse-grained force field to simulate monolayers containing pure dipalmitoylphosphatidylcholine (DPPC) and DPPC mixed with palmitoyloleoylphosphatidylglycerol (POPG), palmitic acid (PA), and/or peptides. The peptides considered include the 25-residue N-terminal fragment of SP-B (SP-B(1-25)), SP-C, and several SP-B(1-25) mutants in which charged and hydrophilic residues are replaced by hydrophobic ones, or vice-versa. We observe two folding mechanisms: folding by the amplification of undulations and folding by nucleation about a defect. The first mechanism is observed in monolayers containing either POPG or peptides, while the second mechanism is observed only with peptides present, and involves the lipid-mediated aggregation of the peptides into a defect, from which the fold can nucleate. Fold nucleation from a defect displays a dependence on the hydrophobic character of the peptides; if the number of hydrophobic residues is decreased significantly, monolayer folding does not occur. The addition of POPG or peptides to the DPPC monolayer has a fluidizing effect, which assists monolayer folding. In contrast, the addition of PA has a charge-dependent condensing affect on DPPC monolayers containing SP-C. The peptides appear to play a significant role in the folding process, and provide a larger driving force for folding than POPG. In addition to promoting fold formation, the peptides also display fusogenic behavior, which can lead to surface refining.
authors.affiliation: Dept. of Chemical Engineering, University of Michigan, 2300 Hayward St., 3074 H.H. Dow Building, Ann Arbor, Michigan 48109, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Duncan
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Larson
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry*; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry*; D013500:Surface Tension; D013696:Temperature
chemical_list: D010446:Peptide Fragments; D010715:Phosphatidylglycerols; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D015060:1,2-Dipalmitoylphosphatidylcholine; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol