Abstract
In this review, we discuss the use of small-angle X-ray diffraction approaches in studying the formation of cholesterol crystalline domains in membranes derived from model and biological sources. Numerous studies have shown that monomeric cholesterol can self-associate and form immiscible, membrane-restricted domains as a result of increased membrane concentration or systematic oxidation of membrane phospholipids. These domains are observed, in an X-ray diffraction pattern, as reflections describing a unit cell periodicity of 34 Å, which is consistent with cholesterol molecules arranged in a tail-to-tail, bilayer conformation. In vascular smooth muscle cells isolated from animal models of atherosclerosis, plasmalemmal cholesterol domain formation is associated with cellular dysfunction, including the disruption of calcium transport mechanisms. Cholesterol domains are also observed in macrophages and precede the deposition of extracellular cholesterol crystals in the atheroma. We have also shown that cholesterol domains can be produced in model membranes following exposure to oxidative stress and other disease-like conditions such as hyperglycemia. By contrast, cholesterol domains appear to be essential to the normal physiology of certain cell groups such as those of the human ocular lens. Cholesterol domains are a prominent structural feature of the lens fiber cell plasma membrane where they are believed to facilitate lens tissue transparency and interfere with various mechanisms of cataract formation. These contrasting biologic effects highlight the complex role that cholesterol domains play in cell plasma membrane structure-function relationships in both health and disease.
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Bach D, Borochov N, Wachtel E (1998) Phase separation of cholesterol in dimyristoyl phosphatidylserine cholesterol mixtures. Chem Phys Lipids 92:71–77
Bialecki RA, Tulenko TN (1989) Excess membrane cholesterol alters calcium channels in arterial smooth muscle. Am J Physiol 257:C306–C314
Blaurock AE (1971) Structure of the nerve myelin membrane: proof of the low-resolution profile. J Mol Biol 56:35–52
Blaurock AE (1982) Evidence of bilayer structure and of membrane interactions from X-ray diffraction analysis. Biochim Biophys Acta 650:167–207
Blaurock AE, Wilkins MH (1972) Structure of retinal photoreceptor membranes. Nature 236:313–314
Bloom M, Thewalt JL (1995) Time and distance scales of membrane domain organization. Mol Membr Biol 12:9–13
Bolotina V, Gericke M, Bregestovski P (1991) Kinetic differences between Ca(2+)-dependent K+ channels in smooth muscle cells isolated from normal and atherosclerotic human aorta. Proc Biol Sci 244:51–55
Borchman D, Cenedella RJ, Lamba OP (1996) Role of cholesterol in the structural order of lens membrane lipids. Exp Eye Res 62:191–197
Bretscher MS, Munro S (1993) Cholesterol and the Golgi apparatus. Science 261:1280–1281
Broderick R, Bialecki R, Tulenko TN (1989) Cholesterol-induced changes in rabbit arterial smooth muscle sensitivity to adrenergic stimulation. Am J Physiol 257:H170–H178
Broekhuyse RM, Soeting WJ (1976) Lipids in tissues of the eye. XV. Essential fatty acids in lens lipids. Exp Eye Res 22:653–657
Brown DA, London E (2000) Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem 275:17221–17224
Byrdwell WC, Borchman D (1997) Liquid chromatography/mass-spectrometric characterization of sphingomyelin and dihydrosphingomyelin of human lens membranes. Ophthalmic Res 29:191–206
Byrdwell WC, Borchman D, Porter RA, Taylor KG, Yappert MC (1994) Separation and characterization of the unknown phospholipid in human lens membranes. Invest Ophthalmol Vis Sci 35:4333–4343
Cenedella RJ, Bierkamper GG (1979) Mechanism of cataract production by 3-beta(2-diethylaminoethoxy) androst-5-en-17-one hydrochloride, U18666A: An inhibitor of cholesterol biosynthesis. Exp Eye Res 28:673–688
Chandrasekher G, Cenedella RJ (1995) Protein associated with human lens ‘native’ membrane during aging and cataract formation. Exp Eye Res 60:707–717
Chang HM, Reitstetter R, Mason RP, Gruener R (1995) Attenuation of channel kinetics and conductance by cholesterol: An interpretation using structural stress as a unifying concept. J Membr Biol 143:51–63
Chen M, Mason RP, Tulenko TN (1995) Atherosclerosis alters the composition, structure and function of arterial smooth muscle cell plasma membranes. Biochim Biophys Acta 1272:101–112
Corless JM (1972) Lamellar structure of bleached and unbleached rod photoreceptor membranes. Nature 237:229–231
Craven BM (1976) Crystal structure of cholesterol monohydrate. Nature 260:727–729
Dupont Y, Hasselbach W (1973) Structural changes in sarcoplasmic reticulum membrane induced by SH reagents. Nat New Biol 246:41–44
Edidin M (1997) Lipid microdomains in cell surface membranes. Curr Opin Struct Biol 7:528–532
Engelman DM, Rothman JE (1972) The planar organization of lecithin-cholesterol bilayers. J Biol Chem 247:3694–3697
Epand RM, Maekawa S, Yip CM, Epand RF (2001) Protein-induced formation of cholesterol-rich domains. Biochemistry 40:10514–10521
Franks NP, Levine YK (1981) Low-angle X-ray diffraction. Mol Biol Biochem Biophys 31:437–487
Geng YJ, Phillips JE, Mason RP, Casscells SW (2003) Cholesterol crystallization and macrophage apoptosis: Implication for atherosclerotic plaque instability and rupture. Biochem Pharmacol 66:1485–1492
Gleason MM, Medow MS, Tulenko TN (1991) Excess membrane cholesterol alters calcium movements, cytosolic calcium levels, and membrane fluidity in arterial smooth muscle cells. Circ Res 69:216–227
Harris JS, Epps DE, Davio SR, Kezdy FJ (1995) Evidence for transbilayer, tail-to-tail cholesterol dimers in dipalmitoylglycerophosphocholine liposomes. Biochemistry 34:3851–3857
Houslay MD, Stanley KK (1982) Dynamics of biological membranes: influence on synthesis, structure and function. John Wiley, New York
Hui SW (1995) Geometry of domains and domain boundaries in monolayers and bilayers. Mol Membr Biol 12:45–50
Jacob RF, Mason RP (2005) Lipid peroxidation induces cholesterol domain formation in model membranes. J Biol Chem 280:39380–39387
Jacob RF, Cenedella RJ, Mason RP (1999) Direct evidence for immiscible cholesterol domains in human ocular lens fiber cell plasma membranes. J Biol Chem 274:31613–31618
Jacob RF, Aleo MD, Self-Medlin Y, Doshna CM, Mason RP (2013) 1,2-Naphthoquinone stimulates lipid peroxidation and cholesterol domain formation in model membranes. Invest Ophthalmol Vis Sci 54:7189–7197
Janes PW, Ley SC, Magee AI, Kabouridis PS (2000) The role of lipid rafts in T cell antigen receptor (TCR) signalling. Semin Immunol 12:23–34
Katz SS, Small DM, Smith FR, Dell RB, Goodman DS (1982) Cholesterol turnover in lipid phases of human atherosclerotic plaque. J Lipid Res 23:733–737
Kellner-Weibel G, Yancey PG, Jerome WG, Walser T, Mason RP, Phillips MC, Rothblat GH (1999) Crystallization of free cholesterol in model macrophage foam cells. Arterioscler Thromb Vasc Biol 19:1891–1898
Kirschner DA, Caspar DL (1972) Comparative diffraction studies on myelin membranes. Ann N Y Acad Sci 195:309–320
Knutton S, Finean JB, Coleman R, Limbrick AR (1970) Low-angle X-ray diffraction and electronmicroscope studies of isolated erythrocyte membranes. J Cell Sci 7:357–371
Langlet C, Bernard AM, Drevot P, He HT (2000) Membrane rafts and signaling by the multichain immune recognition receptors. Curr Opin Immunol 12:250–255
Lau YT (1994) Cholesterol enrichment inhibits Na+/K+ pump in endothelial cells. Atherosclerosis 110:251–257
Leonard A, Dufourc EJ (1991) Interactions of cholesterol with the membrane lipid matrix: a solid state NMR approach. Biochimie 73:1295–1302
Li LK, So L, Spector A (1985) Membrane cholesterol and phospholipid in consecutive concentric sections of human lenses. J Lipid Res 26:600–609
Li LK, So L, Spector A (1987) Age-dependent changes in the distribution and concentration of human lens cholesterol and phospholipids. Biochim Biophys Acta 917:112–120
Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874
Liscum L, Underwood KW (1995) Intracellular cholesterol transport and compartmentation. J Biol Chem 270:15443–15446
Maekawa S, Sato C, Kitajima K, Funatsu N, Kumanogoh H, Sokawa Y (1999) Cholesterol-dependent localization of NAP-22 on a neuronal membrane microdomain (raft). J Biol Chem 274:21369–21374
Mason RP, Walter MF, Day CA, Jacob RF (2006) Active metabolite of atorvastatin inhibits membrane cholesterol domain formation by an antioxidant mechanism. J Biol Chem 281:9337–9345
McIntosh TJ (1978) The effect of cholesterol on the structure of phosphatidylcholine bilayers. Biochim Biophys Acta 513:43–58
Moody MF (1963) X-ray diffraction pattern of nerve myelin: a method for determining the phases. Science 142:1173–1174
Mukherjee S, Chattopadhyay A (1996) Membrane organization at low cholesterol concentrations: a study using 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled cholesterol. Biochemistry 35:1311–1322
Ostermeyer AG, Beckrich BT, Ivarson KA, Grove KE, Brown DA (1999) Glycosphingolipids are not essential for formation of detergent- resistant membrane rafts in melanoma cells. Methyl-beta-cyclodextrin does not affect cell surface transport of a GPI-anchored protein. J Biol Chem 274:34459–34466
Phillips MC, Johnson WC, Rothblat GH (1997) Mechanism and consequences of cellular cholesterol exchange and transfer. Biochim Biophys Acta 906:223–276
Phillips JE, Geng YJ, Mason RP (2001) 7-Ketocholesterol forms crystalline domains in model membranes and murine aortic smooth muscle cells. Atherosclerosis 159:125–135
Rafferty NS (1985) Lens morphology. In: Maisel H (ed) The Ocular Lens. Marcel Dekker, New York, pp 1–60
Rice PA, McConnell HM (1989) Critical shape transitions of monolayer lipid domains. Proc Natl Acad Sci U S A 86:6445–6448
Ruocco MJ, Shipley GG (1984) Interaction of cholesterol with galactocerebroside and galactocerebroside-phosphatidylcholine bilayer membranes. Biophys J 46:695–707
Schroeder F, Wood WG (1995) Lateral lipid domains and membrane function. In: Sperelakis N (ed) Cell Physiology Source Book. Academic, New York, pp 36–44
Schroeder F, Jefferson JR, Kier AB, Knittel J, Scallen TJ, Wood WG, Hapala I (1991) Membrane cholesterol dynamics: cholesterol domains and kinetic pools. Proc Soc Exp Biol Med 196:235–252
Schroeder F, Woodford JK, Kavecansky J, Wood WG, Joiner C (1995) Cholesterol domains in biological membranes. Mol Membr Biol 12:113–119
Self-Medlin Y, Byun J, Jacob RF, Mizuno Y, Mason RP (2009) Glucose promotes membrane cholesterol crystalline domain formation by lipid peroxidation. Biochim Biophys Acta 1788:1398–1403
Shinitzky M, Inbar M (1976) Microviscosity parameters and protein mobility in biological membranes. Biochim Biophys Acta 433:133–149
Shrivastava S, Pucadyil TJ, Paila YD, Ganguly S, Chattopadhyay A (2010) Chronic cholesterol depletion using statin impairs the function and dynamics of human serotonin(1A) receptors. Biochemistry 49:5426–5435
Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572
Simons K, Ikonen E (2000) How cells handle cholesterol. Science 290:1721–1726
Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31–39
Slotte JP (1995a) Lateral domain formation in mixed monolayers containing cholesterol and dipalmitoylphosphatidylcholine or N-palmitoylsphingomyelin. Biochim Biophys Acta 1235:419–427
Slotte PJ (1995b) Effect of sterol structure on molecular interactions and lateral domain formation in monolayers containing dipalmitoyl phosphatidylcholine. Biochim Biophys Acta 1237:127–134
Small DM (1988) Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry. Arterioscler Thromb Vasc Biol 8:103–129
Tocanne JF (1992) Detection of lipid domains in biological membranes. Comments Mol Cell Biophys 8:53–72
Tulenko TN, Chen M, Mason PE, Mason RP (1998) Physical effects of cholesterol on arterial smooth muscle membranes: evidence of immiscible cholesterol domains and alterations in bilayer width during atherogenesis. J Lipid Res 39:947–956
Worthington CR, Liu SC (1973) Structure of sarcoplasmic reticulum membranes at low resolution (17Å). Arch Biochem Biophys 157:573–579
Yeagle PL (1985) Cholesterol and the cell membrane. Biochim Biophys Acta 822:267–287
Yeagle PL, Young J, Rice D (1988) Effects of cholesterol on (Na+, K+)-ATPase ATP hydrolyzing activity in bovine kidney. Biochemistry 27:6449–6452
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Mason, R.P., Jacob, R.F. (2015). Characterization of Cholesterol Crystalline Domains in Model and Biological Membranes Using X-Ray Diffraction. In: Chakrabarti, A., Surolia, A. (eds) Biochemical Roles of Eukaryotic Cell Surface Macromolecules. Advances in Experimental Medicine and Biology, vol 842. Springer, Cham. https://doi.org/10.1007/978-3-319-11280-0_15
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