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Effects of cholesterol on the structure and collapse of DPPC monolayers

      Abstract

      Cholesterol induces faster collapse by compressed films of pulmonary surfactant. Because collapse prevents films from reaching the high surface pressures achieved in the alveolus, most therapeutic surfactants remove or omit cholesterol. The studies here determined the structural changes by which cholesterol causes faster collapse by films of dipalmitoyl phosphatidylcholine, used as a simple model for the functional alveolar film. Measurements of isobaric collapse, with surface pressure held constant at 52 mN/m, showed that cholesterol had little effect until the mol fraction of cholesterol, Xchol, exceeded 0.20. Structural measurements of grazing incidence X-ray diffraction at ambient laboratory temperatures and a surface pressure of 44 mN/m, just below the onset of collapse, showed that the major structural change in an ordered phase occurred at lower Xchol. A centered rectangular unit cell with tilted chains converted to an untilted hexagonal structure over the range of Xchol = 0.0–0.1. For Xchol = 0.1–0.4, the ordered structure was nearly invariant; the hexagonal unit cell persisted, and the spacing of the chains was essentially unchanged. That invariance strongly suggests that above Xchol = 0.1, cholesterol partitions into a disordered phase, which coexists with the ordered domains. The phase rule requires that for a binary film with coexisting phases, the stoichiometries of the ordered and disordered regions must remain constant. Added cholesterol must increase the area of the disordered phase at the expense of the ordered regions. X-ray scattering from dipalmitoyl phosphatidylcholine/cholesterol fit with that prediction. The data also show a progressive decrease in the size of crystalline domains. Our results suggest that cholesterol promotes adsorption not by altering the unit cell of the ordered phase but by decreasing both its total area and the size of individual crystallites.
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      References

        • Hall S.B.
        • Wang Z.
        • Notter R.H.
        Separation of subfractions of the hydrophobic components of calf lung surfactant.
        J. Lipid Res. 1994; 35: 1386-1394
        • Postle A.D.
        • Heeley E.L.
        • Wilton D.C.
        A comparison of the molecular species compositions of mammalian lung surfactant phospholipids.
        Comp. Biochem. Physiol. A. Mol. Integr. Physiol. 2001; 129: 65-73
        • Bachofen H.
        • Hildebrandt J.
        • Bachofen M.
        Pressure-volume curves of air- and liquid-filled excised lungs-surface tension in situ.
        J. Appl. Physiol. 1970; 29: 422-431
        • Horie T.
        • Hildebrandt J.
        Dynamic compliance, limit cycles, and static equilibria of excised cat lung.
        J. Appl. Physiol. 1971; 31: 423-430
        • Valberg P.A.
        • Brain J.D.
        Lung surface tension and air space dimensions from multiple pressure-volume curves.
        J. Appl. Physiol. 1977; 43: 730-738
        • Schürch S.
        • Goerke J.
        • Clements J.A.
        Direct determination of surface tension in the lung.
        Proc. Natl. Acad. Sci. USA. 1976; 73: 4698-4702
        • Wilson T.A.
        Relations among recoil pressure, surface area, and surface tension in the lung.
        J. Appl. Physiol. 1981; 50: 921-930
        • Schürch S.
        Surface tension at low lung volumes: dependence on time and alveolar size.
        Respir. Physiol. 1982; 48: 339-355
        • Smith J.C.
        • Stamenovic D.
        Surface forces in lungs. I. Alveolar surface tension-lung volume relationships.
        J. Appl. Physiol. 1986; 60: 1341-1350
        • Gaines Jr., G.L.
        Insoluble Monolayers at Liquid-Gas Interfaces.
        Interscience Publishers, 1966: 147
        • Schief W.R.
        • Antia M.
        • Vogel V.
        • et al.
        Liquid-crystalline collapse of pulmonary surfactant monolayers.
        Biophys. J. 2003; 84: 3792-3806
        • Tierney D.F.
        • Johnson R.P.
        Altered surface tension of lung extracts and lung mechanics.
        J. Appl. Physiol. 1965; 20: 1253-1260
        • Hildebran J.N.
        • Goerke J.
        • Clements J.A.
        Pulmonary surface film stability and composition.
        J. Appl. Physiol. 1979; 47: 604-611
        • Notter R.H.
        • Tabak S.A.
        • Mavis R.D.
        Surface properties of binary mixtures of some pulmonary surfactant components.
        J. Lipid Res. 1980; 21: 10-22
        • Enhorning G.
        • Shennan A.
        • Milligan J.
        • et al.
        Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial.
        Pediatrics. 1985; 76: 145-153
        • Fujiwara T.
        • Robertson B.
        Pharmacology of exogenous surfactant.
        in: Robertson B. Golde E.M.G.V. Batenburg J.J. Pulmonary Surfactant: From Molecular Biology to Clinical Practice. Elsevier Science Publishers, 1992: 561-592
        • Bernhard W.
        • Mottaghian J.
        • Poets C.F.
        • et al.
        Commercial versus native surfactants. Surface activity, molecular components, and the effect of calcium.
        Am. J. Respir. Crit. Care Med. 2000; 162: 1524-1533
        • Bartmann P.
        • Bamberger U.
        • Gortner L.
        • et al.
        Immunogenicity and immunomodulatory activity of bovine surfactant (SF-RI 1).
        Acta Paediatr. 1992; 81: 383-388
        • Gortner L.
        • Bernsau U.
        • Reiter H.L.
        • et al.
        A multicenter randomized controlled clinical trial of bovine surfactant for prevention of respiratory distress syndrome.
        Lung. 1990; 168: 864-869
        • Gortner L.
        • Bernsau U.
        • Reiter H.L.
        • et al.
        Does prophylactic use of bovine surfactant change drug utilization in very premature infants during neonatal period?.
        Dev. Pharmacol. Ther. 1991; 16: 1-6
        • Gortner L.
        • Bartmann P.
        • Ball F.
        • et al.
        Early treatment of respiratory distress syndrome with bovine surfactant in very preterm infants: a multicenter controlled clinical trial.
        Pediatr. Pulmonol. 1992; 14: 4-9
        • Woerndle S.
        • Bartmann P.
        The effect of three surfactant preparations on in vitro lymphocyte functions.
        J. Perinat. Med. 1994; 22: 119-128
        • Andersson J.M.
        • Grey C.
        • Sparr E.
        • et al.
        Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract.
        Proc. Natl. Acad. Sci. USA. 2017; 114: E3592-E3601
        • Bangham A.D.
        • Miller N.G.A.
        • Morley C.J.
        • et al.
        Introductory remarks about artificial lung expanding compounds (ALEC).
        Colloids Surf. 1984; 10: 337-341
        • Durand D.J.
        • Clyman R.I.
        • Ballard P.
        • et al.
        Effects of a protein-free, synthetic surfactant on survival and pulmonary function in preterm lambs.
        J. Pediatr. 1985; 107: 775-780
        • Häfner D.
        • Germann P.G.
        • Hauschke D.
        Effects of lung surfactant factor (LSF) treatment on gas exchange and histopathological changes in an animal model of adult respiratory distress syndrome (ARDS): comparison of recombinant LSF with bovine LSF.
        Pulm. Pharmacol. 1994; 7: 319-332
        • Cochrane C.G.
        • Revak S.D.
        Protein-phospholipid interactions in pulmonary surfactant. The Parker B. Francis lectureship.
        Chest. 1994; 105: 57S-62S
        • Robertson B.
        Pathology and pathophysiology of neonatal surfactant deficiency (“respiratory distress syndrome,” “hyaline membrane disease”).
        in: Robertson B. Van Golde L.M.G. Batenburg J.J. Pulmonary Surfactant. Elsevier Science Publishers, 1984: 383-418
        • Gross N.J.
        Pulmonary surfactant: unanswered questions.
        Thorax. 1995; 50: 325-327
        • Kribs A.
        Minimally invasive surfactant therapy and noninvasive respiratory support.
        Clin. Perinatol. 2016; 43: 755-771
        • Cummings J.J.
        • Gerday E.
        • Aero-02 Study I.
        • et al.
        Aerosolized calfactant for newborns with respiratory distress: a randomized trial.
        Pediatrics. 2020; 146: e20193967
        • Gunasekara L.
        • Schürch S.
        • Amrein M.
        • et al.
        Pulmonary surfactant function is abolished by an elevated proportion of cholesterol.
        Biochim. Biophys. Acta. 2005; 1737: 27-35
        • Clements J.A.
        Functions of the alveolar lining.
        Am. Rev. Respir. Dis. 1977; 115: 67-71
        • Bangham A.D.
        • Morley C.J.
        • Phillips M.C.
        The physical properties of an effective lung surfactant.
        Biochim. Biophys. Acta. 1979; 573: 552-556
        • Kaganer V.M.
        • Möhwald H.
        • Dutta P.
        Structure and phase transitions in Langmuir monolayers.
        Rev. Mod. Phys. 1999; 71: 779-819
        • Kahn M.C.
        • Anderson G.J.
        • Hall S.B.
        • et al.
        Phosphatidylcholine molecular species of calf lung surfactant.
        Am. J. Physiol. 1995; 269: L567-L573
        • Markin C.J.
        • Hall S.B.
        The anionic phospholipids of bovine pulmonary surfactant.
        Lipids. 2021; 56: 49-57
        • Putz G.
        • Goerke J.
        • Clements J.A.
        • et al.
        Evaluation of pressure-driven captive bubble surfactometer.
        J. Appl. Physiol. 1994; 76: 1417-1424
        • Crane J.M.
        • Putz G.
        • Hall S.B.
        Persistence of phase coexistence in disaturated phosphatidylcholine monolayers at high surface pressures.
        Biophys. J. 1999; 77: 3134-3143
        • Khoojinian H.
        • Goodarzi J.P.
        • Hall S.B.
        Optical factors in the rapid analysis of captive bubbles.
        Langmuir. 2012; 28: 14081-14089
        • Rugonyi S.
        • Smith E.C.
        • Hall S.B.
        Transformation diagrams for the collapse of a phospholipid monolayer.
        Langmuir. 2004; 20: 10100-10106
        • Smith E.C.
        • Crane J.M.
        • Hall S.B.
        • et al.
        Metastability of a supercompressed fluid monolayer.
        Biophys. J. 2003; 85: 3048-3057
        • Smith E.C.
        • Laderas T.G.
        • Hall S.B.
        • et al.
        Persistence of metastability after expansion of a supercompressed fluid monolayer.
        Langmuir. 2004; 20: 4945-4953
        • Crane J.M.
        • Hall S.B.
        Rapid compression transforms interfacial monolayers of pulmonary surfactant.
        Biophys. J. 2001; 80: 1863-1872
        • Smith R.D.
        • Berg J.C.
        The collapse of surfactant monolayers at the air-water interface.
        J. Colloid Interface Sci. 1980; 74: 273-286
        • Als-Nielsen J.
        • Jacquemain D.
        • Leiserowitz L.
        • et al.
        Principles and applications of grazing incidence X-ray and neutron scattering from ordered molecular monolayers at the air-water interface.
        Phys. Rep. 1994; 246: 251-313
        • Borie B.
        X-ray diffraction in crystals, imperfect crystals, and amorphous bodies.
        J. Am. Chem. Soc. 1965; 87: 140-141
        • Tippmann-Krayer P.
        • Moehwald H.
        Precise determination of tilt angles by X-ray diffraction and reflection with arachidic acid monolayers.
        Langmuir. 1991; 7: 2303-2306
        • Colacicco G.
        • Basu M.K.
        Effects of cholesterol and cholesteryl ester on dynamic surface tension of dipalmitoyl lecithin.
        J. Colloid Interface Sci. 1977; 61: 516-518
        • Ivankin A.
        • Kuzmenko I.
        • Gidalevitz D.
        Cholesterol-phospholipid interactions: new insights from surface x-ray scattering data.
        Phys. Rev. Lett. 2010; 104: 108101
        • Callen H.B.
        Thermodynamics; an Introduction to the Physical Theories of Equilibrium Thermostatics and Irreversible Thermodynamics.
        Wiley, 1960: 163-167
        • Rapp B.
        • Gruler H.
        Phase-transitions in thin smectic films at the air-water interface.
        Phys. Rev. A. 1990; 42: 2215-2218
        • Ipsen J.H.
        • Karlström G.
        • Zuckermann M.J.
        • et al.
        Phase equilibria in the phosphatidylcholine-cholesterol system.
        Biochim. Biophys. Acta. 1987; 905: 162-172
        • McConnell H.M.
        • Vrljic M.
        Liquid-liquid immiscibility in membranes.
        Annu. Rev. Biophys. Biomol. Struct. 2003; 32: 469-492
        • Keating E.
        • Rahman L.
        • Petersen N.O.
        • et al.
        Effect of cholesterol on the biophysical and physiological properties of a clinical pulmonary surfactant.
        Biophys. J. 2007; 93: 1391-1401