title: Lipid composition greatly affects the in vitro surface activity of lung surfactant protein mimics.
abstract: A crucial aspect of developing a functional, biomimetic lung surfactant (LS) replacement is the selection of the synthetic lipid mixture and surfactant proteins (SPs) or suitable mimics thereof. Studies elucidating the roles of different lipids and surfactant proteins in natural LS have provided critical information necessary for the development of synthetic LS replacements that offer performance comparable to the natural material. In this study, the in vitro surface-active behaviors of peptide- and peptoid-based mimics of the lung surfactant proteins, SP-B and SP-C, were investigated using three different lipid formulations. The lipid mixtures were chosen from among those commonly used for the testing and characterization of SP mimics--(1) dipalmitoyl phosphatidylcholine:palmitoyloleoyl phosphatidylglycerol 7:3 (w/w) (PCPG), (2) dipalmitoyl phosphatidylcholine:palmitoyloleoyl phosphatidylglycerol:palmitic acid 68:22:9 (w/w) (TL), and (3) dipalmitoyl phosphatidylcholine:palmitoyloleoyl phosphatidylcholine:palmitoyloleoyl phosphatidylglycerol:palmitoyloleoyl phosphatidylethanolamine:palmitoyloleoyl phosphatidylserine:cholesterol 16:10:3:1:3:2 (w/w) (IL). The lipid mixtures and lipid/peptide or lipid/peptoid formulations were characterized in vitro using a Langmuir-Wilhelmy surface balance, fluorescent microscopic imaging of surface film morphology, and a pulsating bubble surfactometer. Results show that the three lipid formulations exhibit significantly different surface-active behaviors, both in the presence and absence of SP mimics, with desirable in vitro biomimetic behaviors being greatest for the TL formulation. Specifically, the TL formulation is able to reach low-surface tensions at physiological temperature as determined by dynamic PBS and LWSB studies, and dynamic PBS studies show this to occur with a minimal amount of compression, similar to natural LS.
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Seurynck-Servoss
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Dohm
authors.forename: Cindy W
authors.initials: CW
authors.lastname: Wu
authors.forename: Annelise E
authors.initials: AE
authors.lastname: Barron
mesh_terms: D006801:Humans; D007231:Infant, Newborn; D008856:Microscopy, Fluorescence; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry; D010658:Phenylglyoxal / Q000031:analogs & derivatives / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry*; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000737:chemistry*; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism; D013499:Surface Properties
chemical_list: D010455:Peptides; D010743:Phospholipids; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; C031665:4-carboxyphenylglyoxal; D010658:Phenylglyoxal