Lipid-Protein Interactions Alter Line Tensions and Domain Size Distributions in Lung Surfactant Monolayers

Dhar, Prajnaparamita; Eck, Elizabeth; Israelachvili, Jacob N.; Lee, Dong Woog; Min, Younjin; Ramachandran, Arun; Waring, Alan J.; Zasadzinski, Joseph A.

doi:10.1016/j.bpj.2011.11.4007

Cited by 44 publications

(91 citation statements)

References 59 publications

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“…5 shows the surface morphology of the LE-LC phase of DPPC on CaCl 2 and MgCl 2 solutions at 0.3, 1.0, and 2.0 M. On 0.3 M CaCl 2 solutions DPPC forms domains that are on average less than half the size as those on water. The number density of LC domains increases by fivefold relative to water (Table 1), and domains are circular in shape instead of multilobed, indicating that an increase in line tension occurs in the presence of Ca 2+ [66]. The decrease in size and increase in number density is consistent with fluorescence microscopy studies of DPPC on CaCl 2 solutions (61.0 M) [40,53].…”

Section: Cation Identity and Salt Concentration Effects On The Surfacsupporting

confidence: 80%

Effect of cation enrichment on dipalmitoylphosphatidylcholine (DPPC) monolayers at the air-water interface

Adams

Casper

Allen

2016

Journal of Colloid and Interface Science

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The effect of highly concentrated salt solutions of marine-relevant cations (Na(+), K(+), Mg(2+), and Ca(2+)) on Langmuir monolayers of dipalmitoylphosphatidylcholine (DPPC) was investigated by means of surface pressure-area isotherms, Brewster angle microscopy (BAM), and infrared reflection-absorption spectroscopy (IRRAS). It was found that monovalent cations and Mg(2+) have similar phase behavior, causing DPPC monolayers to expand, while Ca(2+) induces condensation. All cations disrupted the surface morphology at high cation concentration, resulting in decreased reflectivity from the monolayer. Monolayer refractive index was calculated from BAM image intensity in the liquid condensed phase and decreased with increasing cation concentration, which suggests that orientation of the alkyl chains change. Monovalent ions increase ordering of the alkyl chains, more than divalents, yet have little interaction with the DPPC headgroup. Mg(2+) induces gauche defects in the alkyl chain and increases headgroup hydration at low lipid coverage but increases chain ordering and dehydrates the headgroup at high lipid coverage. Ca(2+) orders alkyl chains and dehydrates the phosphate moiety, independent of lipid phase. At the highest salt concentration investigated, significant narrowing of the asymmetric PO2(-) vibrational mode occurs and is attributed to considerable dehydration of the DPPC headgroup.

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Section: Cation Identity and Salt Concentration Effects On The Surfacsupporting

confidence: 80%

Effect of cation enrichment on dipalmitoylphosphatidylcholine (DPPC) monolayers at the air-water interface

Adams

Casper

Allen

2016

Journal of Colloid and Interface Science

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“…In the absence of a DPPC monolayer, Rh123 had a featureless lateral distribution as it was uniformly distributed in the subphase. The shape, size, and number density of the LC domains remained the same as with the lipid-conjugated TR, suggesting that Rh123 did not alter either the line tension between the phases or the local dipole density difference (23,39).…”

mentioning

confidence: 70%

Visualizing monolayers with a water-soluble fluorophore to quantify adsorption, desorption, and the double layer

Shieh

Zasadzinski

2015

Proc. Natl. Acad. Sci. U.S.A.

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Contrast in confocal microscopy of phase-separated monolayers at the air-water interface can be generated by the selective adsorption of water-soluble fluorescent dyes to disordered monolayer phases. Optical sectioning minimizes the fluorescence signal from the subphase, whereas convolution of the measured point spread function with a simple box model of the interface provides quantitative assessment of the excess dye concentration associated with the monolayer. Coexisting liquid-expanded, liquid-condensed, and gas phases could be visualized due to differential dye adsorption in the liquid-expanded and gas phases. Dye preferentially adsorbed to the liquid-disordered phase during immiscible liquid-liquid phase coexistence, and the contrast persisted through the critical point as shown by characteristic circle-to-stripe shape transitions. The measured dye concentration in the disordered phase depended on the phase composition and surface pressure, and the dye was expelled from the film at the end of coexistence. The excess concentration of a cationic dye within the double layer adjacent to an anionic phospholipid monolayer was quantified as a function of subphase ionic strength, and the changes in measured excess agreed with those predicted by the mean-field Gouy-Chapman equations. This provided a rapid and noninvasive optical method of measuring the fractional dissociation of lipid headgroups and the monolayer surface potential.lipid domains | lung surfactants | surface potential | phase behavior L ipid monolayers have long been used as a simplified model for cell membranes (1-4), especially for the study of 2D phase separation that may underlie the raft hypothesis of cell membrane organization (5-8). Monolayers are also of interest in the physics of ordering and dynamic processes in two dimensions such as the structure and flow of hexatic phases (9-11). Additionally, all air-breathing mammals have a lipid-protein monolayer lining the lung alveoli to minimize surface tension effects on breathing; deficiency or disruption of this monolayer leads to potentially fatal respiratory distress syndrome in infants and adults (12, 13). The general acceptance of complex monolayer and bilayer phase behavior, especially phase coexistence (14-16) and critical phenomena (7,8,17,18), has relied on the visualization of fluorescently tagged lipids segregated between phases in the monolayer. This segregation, due to differences in local molecular organization, provides the necessary contrast to visualize even subtle differences in packing density, molecular tilt, and short-and long-range ordering. Since the technique was introduced (14,(19)(20)(21), visualization of the distribution of labeled lipids has settled numerous debates over the molecular organization of monolayers (2, 4, 22, 23) and bilayers (8, 24).However, fluorescently tagged lipids, like many of the other lipids in monolayers and bilayers, are effectively insoluble in the surrounding aqueous subphase and are trapped in the monolayer or bilayer. As a result, expelling ...

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“…Therefore in the absence of cellular injury, AgNPs acutely increase the work of breathing possibly via direct interactions with components of the lung lining fluid. The lung lining fluid comprises a complex mixture of lipids and proteins that regulate both surface tension and innate immunity (Atochina-Vasserman et al, 2009; Dhar et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

“…The respiratory system is a primary target for exposure (Bakshi et al, 2008). Although numerous studies have examined particle–particle interactions in various media and particle–surfactant interactions in vitro and in vivo (Dhar et al, 2012; Foldbjerg et al, 2011; Leo et al, 2013; Salvador-Morales et al, 2007; Tatur & Badia, 2012), potential effects on the organ-level physiology and toxicity at low doses of AgNPs are still poorly understood and these doses may more accurately reflect real world exposure.…”

Section: Introductionmentioning

confidence: 99%

Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity

et al. 2015

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Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 µg/g body weight) 20 and 110nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

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Lipid-Protein Interactions Alter Line Tensions and Domain Size Distributions in Lung Surfactant Monolayers

Cited by 44 publications

References 59 publications

Effect of cation enrichment on dipalmitoylphosphatidylcholine (DPPC) monolayers at the air-water interface

Effect of cation enrichment on dipalmitoylphosphatidylcholine (DPPC) monolayers at the air-water interface

Visualizing monolayers with a water-soluble fluorophore to quantify adsorption, desorption, and the double layer

Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity

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