Biliary cholesterol crystallization characterized by single-crystal cryogenic electron diffraction

Daphne Weihs, Judith Schmidt, Ilana Goldiner, Dganit Danino, Moshe Rubin, Yeshayahu Talmon*, Fred M. Konikoff

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Cholesterol crystals are the building blocks of cholesterol gallstones. The exact structure of early-forming crystals is still controversial. We combined cryogenic-temperature transmission electron microscopy with cryogenic- temperature electron diffraction to sequentially study crystal development and structure in nucleating model and native gallbladder biles. The growth and long-term stability of classic cholesterol monohydrate (ChM) crystals in native and model biles was determined. In solutions of model bile with low phospholipid-to-cholesterol ratio, electron diffraction provided direct proof of a novel transient polymorph that had an elongated habit and unit cell parameters differing from those of classic triclinic ChM. This crystal is exactly the monoclinic ChM phase described by Solomonov and coworkers (Biophysical J., In press) in cholesterol monolayers compressed on the air-water interface. We observed no evidence of anhydrous cholesterol crystallization in any of the biles studied. In conclusion, classic ChM is the predominant and stable form in native and model biles. However, under certain (low phospholipid) conditions, transient intermediate polymorphs may form. These findings, documenting single-crystal analysis in bulk solution, provide an experimental approach to investigating factors influencing biliary cholesterol crystal nucleation and growth as well as other processes of nucleation and crystallization in liquid systems.

Original languageEnglish
Pages (from-to)942-948
Number of pages7
JournalJournal of Lipid Research
Issue number5
StatePublished - 2005
Externally publishedYes


  • Anhydrous cholesterol
  • Bile
  • Cholesterol monohydrate
  • Gallstones


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