Complete mapping of crystallization pathways during cholesterol precipitation from model bile: Influence of physical-chemical variables of pathophysiologic relevance and identification of a stable liquid crystalline state in cold, dilute and hydrophilic bile salt-containing systems

David Q.H. Wang, Martin C. Carey

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159 Citations (Scopus)

Abstract

Using complementary physical-chemical techniques we defined five different crystallization pathways as functions of time (30 days) and increasing lecithin (egg yolk) content in pathophysiologically relevant model biles supersaturated (cholesterol saturation indices, 1.2-2.7) by dilution of ≈29 g/dl bile salt-lecithin-cholesterol micellar solutions. As evidenced by quasi-elastic light-scattering spectroscopy, supersaturation was heralded by the appearance of unilamellar vesicles. With the lowest lecithin contents, arc-like crystals with habit and density (d 1.030 g/mL) consistent with anhydrous cholesterol appeared first and evolved via helical and tubular crystals to form plate-like cholesterol monohydrate crystals (d 1.045 g/mL). With higher lecithin fractions, cholesterol monohydrate crystals appeared earlier than arc and other transitional crystals. With typical physiological lecithin contents, early liquid crystals (d 1.020 g/mL) were followed by cholesterol monohydrate crystals and subsequent appearances of arc and other intermediate crystals. With higher lecithin contents, liquid crystals were followed by cholesterol monohydrate crystals only, and at the highest lecithin mole fractions, liquid crystals appeared that did not generate solid crystals. Added calcium increased solid crystal number in proportion to its concentration (5-20 mM) but did not influence appearance times, crystallization pathways, or micellar cholesterol solubilities. Decreases in temperature (37° → 4°C), total lipid concentration (7.3 → 2.4 g/dL), and bile salt hydrophobicity (3α, 12α → 3α,7α → 3α,7α,12α → 3α,7β hydroxylated taurine conjugates) progressively shifted all crystallization pathways to lower lecithin contents, retarded crystallization, and decreased micellar cholesterol solubilities. The lecithin content of mother biles decreased markedly during crystallization especially where liquid crystals were a coexisting phase at equilibrium. This systematic study provides a framework for understanding cholesterol crystallization in human and animal biles and for examining factors that influence the kinetics of phase separation.

Original languageEnglish (US)
Pages (from-to)606-630
Number of pages25
JournalJournal of Lipid Research
Volume37
Issue number3
StatePublished - Mar 1 1996
Externally publishedYes

Fingerprint

Lecithins
Crystallization
Bile Acids and Salts
Bile
Cholesterol
Crystalline materials
Crystals
Liquids
Liquid Crystals
Solubility
Saturation (materials composition)
Unilamellar Liposomes
Egg Yolk
Elastic scattering
Taurine
Supersaturation
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Phase separation
Light scattering

Keywords

  • Calcium
  • Crystal density
  • Crystal habits
  • Gallstones
  • Lecithin
  • Liquid crystals
  • Microscopy
  • Phase diagrams
  • Phospholipid
  • Quasi-elastic light-scattering

ASJC Scopus subject areas

  • Endocrinology

Cite this

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title = "Complete mapping of crystallization pathways during cholesterol precipitation from model bile: Influence of physical-chemical variables of pathophysiologic relevance and identification of a stable liquid crystalline state in cold, dilute and hydrophilic bile salt-containing systems",
abstract = "Using complementary physical-chemical techniques we defined five different crystallization pathways as functions of time (30 days) and increasing lecithin (egg yolk) content in pathophysiologically relevant model biles supersaturated (cholesterol saturation indices, 1.2-2.7) by dilution of ≈29 g/dl bile salt-lecithin-cholesterol micellar solutions. As evidenced by quasi-elastic light-scattering spectroscopy, supersaturation was heralded by the appearance of unilamellar vesicles. With the lowest lecithin contents, arc-like crystals with habit and density (d 1.030 g/mL) consistent with anhydrous cholesterol appeared first and evolved via helical and tubular crystals to form plate-like cholesterol monohydrate crystals (d 1.045 g/mL). With higher lecithin fractions, cholesterol monohydrate crystals appeared earlier than arc and other transitional crystals. With typical physiological lecithin contents, early liquid crystals (d 1.020 g/mL) were followed by cholesterol monohydrate crystals and subsequent appearances of arc and other intermediate crystals. With higher lecithin contents, liquid crystals were followed by cholesterol monohydrate crystals only, and at the highest lecithin mole fractions, liquid crystals appeared that did not generate solid crystals. Added calcium increased solid crystal number in proportion to its concentration (5-20 mM) but did not influence appearance times, crystallization pathways, or micellar cholesterol solubilities. Decreases in temperature (37° → 4°C), total lipid concentration (7.3 → 2.4 g/dL), and bile salt hydrophobicity (3α, 12α → 3α,7α → 3α,7α,12α → 3α,7β hydroxylated taurine conjugates) progressively shifted all crystallization pathways to lower lecithin contents, retarded crystallization, and decreased micellar cholesterol solubilities. The lecithin content of mother biles decreased markedly during crystallization especially where liquid crystals were a coexisting phase at equilibrium. This systematic study provides a framework for understanding cholesterol crystallization in human and animal biles and for examining factors that influence the kinetics of phase separation.",
keywords = "Calcium, Crystal density, Crystal habits, Gallstones, Lecithin, Liquid crystals, Microscopy, Phase diagrams, Phospholipid, Quasi-elastic light-scattering",
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T1 - Complete mapping of crystallization pathways during cholesterol precipitation from model bile

T2 - Influence of physical-chemical variables of pathophysiologic relevance and identification of a stable liquid crystalline state in cold, dilute and hydrophilic bile salt-containing systems

AU - Wang, David Q.H.

AU - Carey, Martin C.

PY - 1996/3/1

Y1 - 1996/3/1

N2 - Using complementary physical-chemical techniques we defined five different crystallization pathways as functions of time (30 days) and increasing lecithin (egg yolk) content in pathophysiologically relevant model biles supersaturated (cholesterol saturation indices, 1.2-2.7) by dilution of ≈29 g/dl bile salt-lecithin-cholesterol micellar solutions. As evidenced by quasi-elastic light-scattering spectroscopy, supersaturation was heralded by the appearance of unilamellar vesicles. With the lowest lecithin contents, arc-like crystals with habit and density (d 1.030 g/mL) consistent with anhydrous cholesterol appeared first and evolved via helical and tubular crystals to form plate-like cholesterol monohydrate crystals (d 1.045 g/mL). With higher lecithin fractions, cholesterol monohydrate crystals appeared earlier than arc and other transitional crystals. With typical physiological lecithin contents, early liquid crystals (d 1.020 g/mL) were followed by cholesterol monohydrate crystals and subsequent appearances of arc and other intermediate crystals. With higher lecithin contents, liquid crystals were followed by cholesterol monohydrate crystals only, and at the highest lecithin mole fractions, liquid crystals appeared that did not generate solid crystals. Added calcium increased solid crystal number in proportion to its concentration (5-20 mM) but did not influence appearance times, crystallization pathways, or micellar cholesterol solubilities. Decreases in temperature (37° → 4°C), total lipid concentration (7.3 → 2.4 g/dL), and bile salt hydrophobicity (3α, 12α → 3α,7α → 3α,7α,12α → 3α,7β hydroxylated taurine conjugates) progressively shifted all crystallization pathways to lower lecithin contents, retarded crystallization, and decreased micellar cholesterol solubilities. The lecithin content of mother biles decreased markedly during crystallization especially where liquid crystals were a coexisting phase at equilibrium. This systematic study provides a framework for understanding cholesterol crystallization in human and animal biles and for examining factors that influence the kinetics of phase separation.

AB - Using complementary physical-chemical techniques we defined five different crystallization pathways as functions of time (30 days) and increasing lecithin (egg yolk) content in pathophysiologically relevant model biles supersaturated (cholesterol saturation indices, 1.2-2.7) by dilution of ≈29 g/dl bile salt-lecithin-cholesterol micellar solutions. As evidenced by quasi-elastic light-scattering spectroscopy, supersaturation was heralded by the appearance of unilamellar vesicles. With the lowest lecithin contents, arc-like crystals with habit and density (d 1.030 g/mL) consistent with anhydrous cholesterol appeared first and evolved via helical and tubular crystals to form plate-like cholesterol monohydrate crystals (d 1.045 g/mL). With higher lecithin fractions, cholesterol monohydrate crystals appeared earlier than arc and other transitional crystals. With typical physiological lecithin contents, early liquid crystals (d 1.020 g/mL) were followed by cholesterol monohydrate crystals and subsequent appearances of arc and other intermediate crystals. With higher lecithin contents, liquid crystals were followed by cholesterol monohydrate crystals only, and at the highest lecithin mole fractions, liquid crystals appeared that did not generate solid crystals. Added calcium increased solid crystal number in proportion to its concentration (5-20 mM) but did not influence appearance times, crystallization pathways, or micellar cholesterol solubilities. Decreases in temperature (37° → 4°C), total lipid concentration (7.3 → 2.4 g/dL), and bile salt hydrophobicity (3α, 12α → 3α,7α → 3α,7α,12α → 3α,7β hydroxylated taurine conjugates) progressively shifted all crystallization pathways to lower lecithin contents, retarded crystallization, and decreased micellar cholesterol solubilities. The lecithin content of mother biles decreased markedly during crystallization especially where liquid crystals were a coexisting phase at equilibrium. This systematic study provides a framework for understanding cholesterol crystallization in human and animal biles and for examining factors that influence the kinetics of phase separation.

KW - Calcium

KW - Crystal density

KW - Crystal habits

KW - Gallstones

KW - Lecithin

KW - Liquid crystals

KW - Microscopy

KW - Phase diagrams

KW - Phospholipid

KW - Quasi-elastic light-scattering

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