TY - JOUR
T1 - Biliary cholesterol crystallization characterized by single-crystal cryogenic electron diffraction
AU - Weihs, Daphne
AU - Schmidt, Judith
AU - Goldiner, Ilana
AU - Danino, Dganit
AU - Rubin, Moshe
AU - Talmon, Yeshayahu
AU - Konikoff, Fred M.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - Anhydrous cholesterol
KW - Bile
KW - Cholesterol monohydrate
KW - Gallstones
UR - http://www.scopus.com/inward/record.url?scp=22144488209&partnerID=8YFLogxK
U2 - 10.1194/jlr.M400458-JLR200
DO - 10.1194/jlr.M400458-JLR200
M3 - 文章
C2 - 15741652
AN - SCOPUS:22144488209
SN - 0022-2275
VL - 46
SP - 942
EP - 948
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 5
ER -