Effects of Cholesterol on Surface Activity and Surface Topography of Spread Surfactant Films

Diemel, Robert V.; Snel, M. M. E.; Golde, L.M.G. Van; Pütz, G.; Haagsman, Henk P.; Batenburg, Joseph J.

doi:10.1021/bi0256532

Cited by 36 publications

(17 citation statements)

References 52 publications

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“…The potential molecular mechanism by which increased levels of cholesterol affect the surface tension reducing ability of surfactant during compression stems mostly from reconstitution studies with high amounts of cholesterol added to exogenous surfactant preparations (8,12,13,18,19). Consistent with our results, addition of 20% cholesterol (by weight) to an exogenous surfactant preparation resulted in an inability to achieve low MST values during the compression phase of dynamic cycling.…”

Section: Discussionsupporting

confidence: 82%

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Vockeroth¹,

Gunasekara

Amrein

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mechanical ventilation may lead to an impairment of the endogenous surfactant system, which is one of the mechanisms by which this intervention contributes to the progression of acute lung injury. The most extensively studied mechanism of surfactant dysfunction is serum protein inhibition. However, recent studies indicate that hydrophobic components of surfactant may also contribute. It was hypothesized that elevated levels of cholesterol significantly contribute to surfactant dysfunction in ventilation-induced lung injury. Sprague-Dawley rats (n = 30) were randomized to either high-tidal volume or low-tidal volume ventilation and monitored for 2 h. Subsequently, the lungs were lavaged, surfactant was isolated, and the biophysical properties of this isolated surfactant were analyzed on a captive bubble surfactometer with and without the removal of cholesterol using methyl-beta-cyclodextrin. The results showed lower oxygenation values in the high-tidal volume group during the last 30 min of ventilation compared with the low-tidal volume group. Surfactant obtained from the high-tidal volume animals had a significant impairment in function compared with material from the low-tidal volume group. Removal of cholesterol from the high-tidal volume group improved the ability of the surfactant to reduce the surface tension to low values. Subsequent reconstitution of high-cholesterol values led to an impairment in surface activity. It is concluded that increased levels of cholesterol associated with endogenous surfactant represent a major contributor to the inhibition of surfactant function in ventilation-induced lung injury.

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Section: Discussionsupporting

confidence: 82%

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Vockeroth¹,

Gunasekara

Amrein

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…AFM examination revealed both samples possessed similar overall structural characteristics at π~30–40 mN/m, including LC micro and nano-domains. These observations are consistent with earlier studies on PL mixtures and natural surfactant extracts [18–21,24,41,47,48]. However, as equilibrium π was approached, only a few bilayer structures were noted with the PL film while numerous bilayer and multilayer stacks were observed with BLES.…”

Section: Discussionsupporting

confidence: 92%

“…With mixed monolayers at low π, an ordered, liquid condensed (LC) phase co-exists with a disordered, liquid expanded (LE) phase [5,16–21]. Dipalmitoylated, gel phase PLs have been shown to exist primarily in the LC phase at physiological temperatures, while unsaturated, fluid phase PL and proteins have been detected exclusively in the LE phase [2,4,14,19,20].…”

Section: Introductionmentioning

confidence: 99%

A modified squeeze-out mechanism for generating high surface pressures with pulmonary surfactant

Keating

Zuo

Tadayyon

et al. 2012

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The exact mechanism by which pulmonary surfactant films reach the very low surface tensions required to stabilize the alveoli at end expiration remains uncertain. We utilized the nanoscale sensitivity of atomic force microscopy (AFM) to examine phospholipid (PL) phase transition and multilayer formation for two Langmuir–Blodgett (LB) systems: a simple 3 PL surfactant-like mixture and the more complex bovine lipid extract surfactant (BLES). AFM height images demonstrated that both systems develop two types of liquid condensed (LC) domains (micro- and nano-sized) within a liquid expanded phase (LE). The 3 PL mixture failed to form significant multilayers at high surface pressure (π while BLES forms an extensive network of multilayer structures containing up to three bilayers. A close examination of the progression of multilayer formation reveals that multilayers start to form at the edge of the solid-like LC domains and also in the fluid-like LE phase. We used the elemental analysis capability of time-of-flight secondary ion mass spectrometry (ToF-SIMS) to show that multilayer structures are enriched in unsaturated PLs while the saturated PLs are concentrated in the remaining interfacial monolayer. This supports a modified squeeze-out model where film compression results in the hydrophobic surfactant protein-dependent formation of unsaturated PL-rich multilayers which remain functionally associated with a monolayer enriched in disaturated PL species. This allows the surface film to attain low surface tensions during compression and maintain values near equilibrium during expansion.

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“…Native surfactant films or films formed from the whole surfactant hydrophobic fraction, including cholesterol, exhibit complex compression-driven lateral transitions, including segregation and remixing of phases, that are profoundly altered when cholesterol is removed (26)(27)(28). Recent studies suggest that physiological levels of cholesterol (up to 10% by weight with respect to phospholipids) may modulate surfactant function (29)(30)(31). The beneficial function of physiological cholesterol levels in surfactant has been clearly established for heterothermic animals, in which the concentration of cholesterol varies rapidly in response to body temperature changes (32).…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Surfactant Protein SP-C Counteracts the Deleterious Effects of Cholesterol on the Activity of Surfactant Films under Physiologically Relevant Compression-Expansion Dynamics

Gómez-Gil

Schürch

Goormaghtigh

et al. 2009

Biophysical Journal

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The presence of cholesterol is critical in defining a dynamic lateral structure in pulmonary surfactant membranes. However, an excess of cholesterol has been associated with impaired surface activity of surfactant. It has also been reported that surfactant protein SP-C interacts with cholesterol in lipid/protein interfacial films. In this study, we analyzed the effect of SP-C on the thermodynamic properties of phospholipid membranes containing cholesterol, and the ability of lipid/protein complexes containing cholesterol to form and respread interfacial films capable of producing very low surface tensions upon repetitive compression-expansion cycling. SP-C modulates the effect of cholesterol to reduce the enthalpy associated with the gel-to-liquid-crystalline melting transition in dipalmitoylphosphatidylcholine (DPPC) bilayers, as analyzed by differential scanning calorimetry. The presence of SP-C affects more subtly the effects of cholesterol on the thermotropic properties of ternary membranes, mimicking more closely the lipid composition of native surfactant, where SP-C facilitates the miscibility of the sterol. Incorporation of 1% or 2% SP-C (protein/phospholipid by weight) promotes almost instantaneous adsorption of suspensions of DPPC/palmitoyloleoylphospatidylcholine (POPC)/palmitoyloleoyl-phosphatidylglycerol (POPG) (50:25:15, w/w/w) into the air-liquid interface of a captive bubble, in both the absence and presence of cholesterol. However, cholesterol impairs the ability of SP-C-containing films to achieve very low surface tensions in bubbles subjected to compression-expansion cycling. Cholesterol also substantially impairs the ability of DPPC/POPC/POPG films containing 1% surfactant protein SP-B to mimic the interfacial behavior of native surfactant films, which are characterized by very low minimum surface tensions with only limited area change during compression and practically no compression-expansion hysteresis. However, the simultaneous presence of 2% SP-C practically restores the compression-expansion dynamics of cholesterol- and SP-B-containing films to the efficient behavior shown in the absence of cholesterol. This suggests that cooperation between the two proteins is required for lipid-protein films containing cholesterol to achieve optimal performance under physiologically relevant compression-expansion dynamics.

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Effects of Cholesterol on Surface Activity and Surface Topography of Spread Surfactant Films

Cited by 36 publications

References 52 publications

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

A modified squeeze-out mechanism for generating high surface pressures with pulmonary surfactant

Pulmonary Surfactant Protein SP-C Counteracts the Deleterious Effects of Cholesterol on the Activity of Surfactant Films under Physiologically Relevant Compression-Expansion Dynamics

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