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However, with age and cataract formation, the concentration of \u03b1ABc in the eye lens cytoplasm decreases, with a corresponding increase in the membrane-bound \u03b1ABc. This study uses the electron paramagnetic resonance (EPR) spin-labeling method to investigate the role of cholesterol (Chol) and Chol bilayer domains (CBDs) in the binding of \u03b1Ac, \u03b1Bc, and \u03b1ABc to the Chol\/model of human lens-lipid (Chol\/MHLL) membranes. The maximum percentage of membrane surface occupied (MMSO) by \u03b1Ac, \u03b1Bc, and \u03b1ABc to Chol\/MHLL membranes at a mixing ratio of 0 followed the trends: MMSO (\u03b1Ac) &gt; MMSO (\u03b1Bc) \u2248 MMSO (\u03b1ABc), indicating that a higher amount of \u03b1Ac binds to these membranes compared to \u03b1Bc and \u03b1ABc. However, with an increase in the Chol concentration in the Chol\/MHLL membranes, the MMSO by \u03b1Ac, \u03b1Bc, and \u03b1ABc decreases until it is completely diminished at a mixing ratio of 1.5. The Ka of \u03b1Ac, \u03b1Bc, and \u03b1ABc to Chol\/MHLL membranes at a mixing ratio of 0 followed the trend: Ka (\u03b1Bc) \u2248 Ka (\u03b1ABc) &gt; Ka (\u03b1Ac), but it was close to zero with the diminished binding at a Chol\/MHLL mixing ratio of 1.5. The mobility near the membrane headgroup regions decreased with \u03b1Ac, \u03b1Bc, and \u03b1ABc binding, and the Chol antagonized the capacity of the \u03b1Ac, \u03b1Bc, and \u03b1ABc to decrease mobility near the headgroup regions. No significant change in membrane order near the headgroup regions was observed, with an increase in \u03b1Ac, \u03b1Bc, and \u03b1ABc concentrations. Our results show that \u03b1Ac, \u03b1Bc, and \u03b1ABc bind differently with Chol\/MHLL membranes at mixing ratios of 0 and 0.5, decreasing the mobility and increasing hydrophobicity near the membrane headgroup region, likely forming the hydrophobic barrier for the passage of polar and ionic molecules, including antioxidants (glutathione), creating an oxidative environment inside the lens, leading to the development of cataracts. However, all binding was completely diminished at a mixing ratio of 1.5, indicating that high Chol and CBDs inhibit the binding of \u03b1Ac, \u03b1Bc, and \u03b1ABc to membranes, preventing the formation of hydrophobic barriers and likely protecting against cataract formation.<\/jats:p>","DOI":"10.3390\/ijms25031923","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T05:22:44Z","timestamp":1707110564000},"page":"1923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cholesterol Content Regulates the Interaction of \u03b1A-, \u03b1B-, and \u03b1-Crystallin with the Model of Human Lens-Lipid Membranes"],"prefix":"10.3390","volume":"25","author":[{"given":"Raju","family":"Timsina","sequence":"first","affiliation":[{"name":"Department of Physics, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-3980","authenticated-orcid":false,"given":"Preston","family":"Hazen","sequence":"additional","affiliation":[{"name":"Biomolecular Sciences Graduate Programs, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1690-1562","authenticated-orcid":false,"given":"Geraline","family":"Trossi-Torres","sequence":"additional","affiliation":[{"name":"Biomolecular Sciences Graduate Programs, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2404-3799","authenticated-orcid":false,"given":"Nawal K.","family":"Khadka","sequence":"additional","affiliation":[{"name":"Department of Physics, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navdeep","family":"Kalkat","sequence":"additional","affiliation":[{"name":"Biomolecular Sciences Graduate Programs, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxman","family":"Mainali","sequence":"additional","affiliation":[{"name":"Department of Physics, Boise State University, Boise, ID 83725, USA"},{"name":"Biomolecular Sciences Graduate Programs, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Bruyne, S., van Schie, L., Himpe, J., De Somer, F., Everaert, I., Derave, W., Van den Broecke, C., Huizing, M., Bostan, N., and Speeckaert, M. (2021). A Potential Role for Fructosamine-3-Kinase in Cataract Treatment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083841"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0140-6736(22)01839-6","article-title":"Cataracts","volume":"401","author":"Cicinelli","year":"2023","journal-title":"Lancet"},{"key":"ref_3","first-page":"86","article-title":"The Ageing Lens","volume":"214","author":"Bron","year":"2000","journal-title":"Ophthalmol. J. Int. Ophtalmol. Int. J. Ophthalmol. Z. Augenheilkd."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.exer.2004.12.007","article-title":"Age-Related Nuclear Cataract-Oxidation Is the Key","volume":"80","author":"Truscott","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.2337\/cd19-0101","article-title":"Prediabetes Deserves More Attention: A Review","volume":"38","author":"Lawal","year":"2020","journal-title":"Clin. Diabetes Publ. Am. Diabetes Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"140","DOI":"10.4239\/wjd.v10.i3.140","article-title":"Cataract in Diabetes Mellitus","volume":"10","author":"Kiziltoprak","year":"2019","journal-title":"World J. Diabetes"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/j.1755-3768.1984.tb03972.x","article-title":"The Prevalence of Cataract in Insulin-Dependent and Non-Insulin-Dependent-Diabetes Mellitus","volume":"62","author":"Nielsen","year":"1984","journal-title":"Acta Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S0161-6420(85)33877-0","article-title":"Prevalence of Cataracts in a Population-Based Study of Persons with Diabetes Mellitus","volume":"92","author":"Klein","year":"1985","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mrugacz, M., Pony-Uram, M., Bryl, A., and Zorena, K. (2023). Current Approach to the Pathogenesis of Diabetic Cataracts. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076317"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.cbi.2014.12.017","article-title":"Aldose Reductase Expression as a Risk Factor for Cataract","volume":"234","author":"Snow","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s13659-020-00290-w","article-title":"Repression of Polyol Pathway Activity by Hemidesmus Indicus Var. Pubescens R.Br. Linn Root Extract, an Aldose Reductase Inhibitor: An In Silico and Ex Vivo Study","volume":"11","author":"Haroon","year":"2021","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1134\/S0006297922020055","article-title":"Effect of Sorbitol on Alpha-Crystallin Structure and Function","volume":"87","author":"Kumar","year":"2022","journal-title":"Biochem. Mosc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000316481","article-title":"Oxidative Damage and the Prevention of Age-Related Cataracts","volume":"44","author":"Beebe","year":"2010","journal-title":"Ophthalmic Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0039-6257(05)80110-9","article-title":"Epidemiology of Risk Factors for Age-Related Cataract","volume":"39","author":"West","year":"1995","journal-title":"Surv. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/S0161-6420(03)00243-4","article-title":"Epidemiologic Study of Age-Related Cataracts among an Elderly Chinese Population in Shih-Pai, Taiwan","volume":"110","author":"Tsai","year":"2003","journal-title":"Ophthalmology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1136\/bjo.2003.038380","article-title":"Risk Factors for Age Related Cataract in a Rural Population of Southern India: The Aravind Comprehensive Eye Study","volume":"88","author":"Nirmalan","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0886-3350(00)00585-X","article-title":"Posterior Subcapsular and Nuclear Cataract after Vitrectomy","volume":"27","author":"Hsuan","year":"2001","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_18","first-page":"84","article-title":"Cataract Formation after Pars Plana Vitrectomy","volume":"17","author":"Chung","year":"2001","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/j.freeradbiomed.2006.07.022","article-title":"Oxidation-Induced Changes in Human Lens Epithelial Cells: 1. Phospholipids","volume":"41","author":"Huang","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1136\/bjo.68.2.113","article-title":"Nuclear Cataract and Myopia during Hyperbaric Oxygen Therapy","volume":"68","author":"Palmquist","year":"1984","journal-title":"Br. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0014-4835(03)00004-6","article-title":"Ultrastructural Characterization and Fourier Analysis of Fiber Cell Cytoplasm in the Hyperbaric Oxygen Treated Guinea Pig Lens Opacification Model","volume":"76","author":"Freel","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0014-4835(77)90256-1","article-title":"Changes in Human Lens Proteins during Nuclear Cataract Formation","volume":"24","author":"Truscott","year":"1977","journal-title":"Exp. Eye Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Timsina, R., and Mainali, L. (2021). Association of Alpha-Crystallin with Fiber Cell Plasma Membrane of the Eye Lens Accompanied by Light Scattering and Cataract Formation. Membranes, 11.","DOI":"10.3390\/membranes11060447"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1006\/exer.1999.0747","article-title":"Age-Related Changes in the Kinetics of Water Transport in Normal Human Lenses","volume":"69","author":"Moffat","year":"1999","journal-title":"Exp. Eye Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"511","DOI":"10.3109\/02713689609000762","article-title":"Levels of Crystallin Fragments and Identification of Their Origin in Water Soluble High Molecular Weight (HMW) Proteins of Human Lenses","volume":"15","author":"Srivastava","year":"1996","journal-title":"Curr. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6664","DOI":"10.1074\/jbc.275.9.6664","article-title":"Characterization of Alpha-Crystallin-Plasma Membrane Binding","volume":"275","author":"Cobb","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.exer.2008.07.001","article-title":"Multi-Crystallin Complexes Exist in the Water-Soluble High Molecular Weight Protein Fractions of Aging Normal and Cataractous Human Lenses","volume":"87","author":"Srivastava","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_28","first-page":"1680","article-title":"Proteomic Analysis of Water Insoluble Proteins from Normal and Cataractous Human Lenses","volume":"13","author":"Harrington","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0014-4835(02)00278-6","article-title":"Alpha-Crystallin","volume":"76","author":"Horwitz","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Santhoshkumar, P., Raju, M., and Sharma, K.K. (2011). \u03b1A-Crystallin Peptide SDRDKFVIFLDVKHF Accumulating in Aging Lens Impairs the Function of \u03b1-Crystallin and Induces Lens Protein Aggregation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019291"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/eye.1999.114","article-title":"Lens \u03b1-Crystallin: Function and Structure","volume":"13","author":"Horwitz","year":"1999","journal-title":"Eye"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.pbiomolbio.2003.11.012","article-title":"Ageing and Vision: Structure, Stability and Function of Lens Crystallins","volume":"86","author":"Bloemendal","year":"2004","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5145","DOI":"10.1167\/iovs.10-5261","article-title":"Large-Scale Binding of \u03b1-Crystallin to Cell Membranes of Aged Normal Human Lenses: A Phenomenon That Can Be Induced by Mild Thermal Stress","volume":"51","author":"Friedrich","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0014-4835(05)80012-0","article-title":"Protein Associated with Human Lens \u201cnative\u201d Membrane during Aging and Cataract Formation","volume":"60","author":"Chandrasekher","year":"1995","journal-title":"Exp. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1021\/bi0112457","article-title":"Alpha-Crystallin Chaperone-like Activity and Membrane Binding in Age-Related Cataracts","volume":"41","author":"Cobb","year":"2002","journal-title":"Biochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.molmed.2012.03.005","article-title":"Protein Misfolding and Aggregation in Cataract Disease and Prospects for Prevention","volume":"18","author":"Moreau","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nature14650","article-title":"Lanosterol Reverses Protein Aggregation in Cataracts","volume":"523","author":"Zhao","year":"2015","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"577","DOI":"10.3109\/02713689609000769","article-title":"EM Immunolocalization of Alpha-Crystallins: Association with the Plasma Membrane from Normal and Cataractous Human Lenses","volume":"15","author":"Boyle","year":"1996","journal-title":"Curr. Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"801","DOI":"10.3109\/02713689209000753","article-title":"Selective Association of Crystallins with Lens \u201cnative\u201d Membrane during Dynamic Cataractogenesis","volume":"11","author":"Cenedella","year":"1992","journal-title":"Curr. Eye Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.exer.2004.12.014","article-title":"\u03b1-Crystallin Binding in Vitro to Lipids from Clear Human Lenses","volume":"81","author":"Grami","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1006\/exer.1997.0467","article-title":"Influence of Cholesterol on the Interaction of Alpha-Crystallin with Phospholipids","volume":"66","author":"Tang","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1006\/exer.1996.0228","article-title":"Properties of \u03b1-Crystallin Bound to Lens Membrane: Probing Organization at the Membrane Surface","volume":"64","author":"Chandrasekher","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1006\/exer.1996.0130","article-title":"Binding Capacity of Alpha-Crystallin to Bovine Lens Lipids","volume":"63","author":"Borchman","year":"1996","journal-title":"Exp. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1006\/exer.1996.0006","article-title":"Lipid \u2013Protein Interactions in Human and Bovine Lens Membranes by Fourier Transform Raman and Infrared Spectroscopies","volume":"62","author":"Sato","year":"1996","journal-title":"Exp. Eye Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1159\/000055571","article-title":"Alpha-Crystallin\/Lens Lipid Interactions Using Resonance Energy Transfer","volume":"31","author":"Tang","year":"1999","journal-title":"Ophthalmic Res."},{"key":"ref_46","first-page":"2798","article-title":"Understanding the \u03b1-Crystallin Cell Membrane Conjunction","volume":"17","author":"Su","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ophtha.2015.10.007","article-title":"Longitudinal Study of Age-Related Cataract Using Dynamic Light Scattering: Loss of \u03b1-Crystallin Leads to Nuclear Cataract Development","volume":"123","author":"Datiles","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_48","first-page":"85","article-title":"Factors Influencing Alpha-Crystallin Association with Phospholipid Vesicles","volume":"8","author":"Cobb","year":"2002","journal-title":"Mol. Vis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.febslet.2013.01.021","article-title":"One Size Doesn\u2019t Fit All: The Oligomeric States of \u03b1B Crystallin","volume":"587","author":"Delbecq","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1146\/annurev-physchem-090419-121428","article-title":"\u03b1-Crystallins in the Vertebrate Eye Lens: Complex Oligomers and Molecular Chaperones","volume":"72","author":"Rocha","year":"2021","journal-title":"Annu. Rev. Phys. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10611","DOI":"10.1073\/pnas.1932958100","article-title":"Polydispersity of a Mammalian Chaperone: Mass Spectrometry Reveals the Population of Oligomers in \u03b1B-Crystallin","volume":"100","author":"Aquilina","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13272","DOI":"10.1073\/pnas.0902651106","article-title":"The Eye Lens Chaperone \u03b1-Crystallin Forms Defined Globular Assemblies","volume":"106","author":"Peschek","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Selivanova, O.M., and Galzitskaya, O.V. (2020). Structural and Functional Peculiarities of \u03b1-Crystallin. Biology, 9.","DOI":"10.3390\/biology9040085"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.bbagen.2009.05.008","article-title":"Lens Aging: Effects of Crystallins","volume":"1790","author":"Sharma","year":"2009","journal-title":"Biochim. Biophys. Acta BBA Gen. Subj."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/iub.373","article-title":"Importance of Eye Lens \u03b1-Crystallin Heteropolymer with 3:1 \u03b1A to \u03b1B Ratio: Stability, Aggregation, and Modifications","volume":"62","author":"Srinivas","year":"2010","journal-title":"IUBMB Life"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"36823","DOI":"10.1074\/jbc.M004233200","article-title":"Differential Protective Activity of \u03b1A- and \u03b1B-Crystallin in Lens Epithelial Cells","volume":"275","author":"Andley","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Phadte, A.S., Sluzala, Z.B., and Fort, P.E. (2021). Therapeutic Potential of \u03b1-Crystallins in Retinal Neurodegenerative Diseases. Antioxidants, 10.","DOI":"10.3390\/antiox10071001"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"21726","DOI":"10.1074\/jbc.M500405200","article-title":"Insights into Hydrophobicity and the Chaperone-like Function of \u03b1A- and \u03b1B-Crystallins: AN ISOTHERMAL TITRATION CALORIMETRIC STUDY","volume":"280","author":"Kumar","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_59","first-page":"205","article-title":"Crystallins, Genes and Cataract","volume":"60","author":"Bhat","year":"2003","journal-title":"Prog. Drug Res. Fortschritte Arzneimittelforschung Progres. Rech. Pharm."},{"key":"ref_60","first-page":"13","article-title":"Alpha-B-Crystallin Expression in Tissues Derived from Different Species in Different Age Groups","volume":"214","author":"Oertel","year":"2000","journal-title":"Ophthalmol. J. Int. Ophtalmol. Int. J. Ophthalmol. Z. Augenheilkd."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/j.1432-1033.1985.tb09253.x","article-title":"Interaction of \u03b1-Crystallin with Lens Plasma Membranes","volume":"152","author":"Mulders","year":"1985","journal-title":"Eur. J. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0014-4835(89)90083-3","article-title":"Loss of High-Affinity Membrane Binding of Bovine Nuclear \u03b1-Crystallin","volume":"49","author":"Mulders","year":"1989","journal-title":"Exp. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"108544","DOI":"10.1016\/j.exer.2021.108544","article-title":"Cholesterol and Cholesterol Bilayer Domains Inhibit Binding of Alpha-Crystallin to the Membranes Made of the Major Phospholipids of Eye Lens Fiber Cell Plasma Membranes","volume":"206","author":"Timsina","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"108337","DOI":"10.1016\/j.exer.2020.108337","article-title":"Interaction of Alpha-Crystallin with Four Major Phospholipids of Eye Lens Membranes","volume":"202","author":"Timsina","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.3109\/02713689309029230","article-title":"High Capacity Binding of Alpha Crystallins to Various Bovine Lens Membrane Preparations","volume":"12","author":"Cenedella","year":"1993","journal-title":"Curr. Eye Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1007\/s12192-019-01021-y","article-title":"The Small Heat Shock Proteins, HSPB1 and HSPB5, Interact Differently with Lipid Membranes","volume":"24","author":"Cauvi","year":"2019","journal-title":"Cell Stress. Chaperones"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1080\/02713683.2022.2040539","article-title":"Alpha-Crystallin Association with the Model of Human and Animal Eye Lens-Lipid Membranes Is Modulated by Surface Hydrophobicity of Membranes","volume":"47","author":"Timsina","year":"2022","journal-title":"Curr. Eye Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Trossi-Torres, G., Timsina, R., and Mainali, L. (2022). Alpha-Crystallin-Membrane Association Modulated by Phospholipid Acyl Chain Length and Degree of Unsaturation. Membranes, 12.","DOI":"10.3390\/membranes12050455"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/0014-4835(92)90026-O","article-title":"Spectroscopic Studies on the Interaction of Calf Lens Membranes with Crystallins","volume":"54","author":"Liang","year":"1992","journal-title":"Exp. Eye Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000055612","article-title":"Age-Related Nuclear Cataract: A Lens Transport Problem","volume":"32","author":"Truscott","year":"2000","journal-title":"Ophthalmic Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1080\/02713683.2016.1231325","article-title":"Changes in the Properties and Organization of Human Lens Lipid Membranes Occurring with Age","volume":"42","author":"Mainali","year":"2017","journal-title":"Curr. Eye Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/0005-2760(87)90291-8","article-title":"Age-Dependent Changes in the Distribution and Concentration of Human Lens Cholesterol and Phospholipids","volume":"917","author":"Li","year":"1987","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1194\/jlr.R004119","article-title":"Lipids and the Ocular Lens","volume":"51","author":"Borchman","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Quinlan, R.A., and Clark, J.I. (2022). Insights into the Biochemical and Biophysical Mechanisms Mediating the Longevity of the Transparent Optics of the Eye Lens. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.102537"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.bbamem.2013.02.006","article-title":"Properties of Membranes Derived from the Total Lipids Extracted from the Human Lens Cortex and Nucleus","volume":"1828","author":"Mainali","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00249-014-1004-7","article-title":"Properties of Membranes Derived from the Total Lipids Extracted from Clear and Cataractous Lenses of 61-70-Year-Old Human Donors","volume":"44","author":"Mainali","year":"2015","journal-title":"Eur. Biophys. J. EBJ"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1038\/s41467-021-22782-0","article-title":"Qki Activates Srebp2-Mediated Cholesterol Biosynthesis for Maintenance of Eye Lens Transparency","volume":"12","author":"Shin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.exer.2018.09.020","article-title":"Detection of Cholesterol Bilayer Domains in Intact Biological Membranes: Methodology Development and Its Application to Studies of Eye Lens Fiber Cell Plasma Membranes","volume":"178","author":"Mainali","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1080\/02713683.2019.1662058","article-title":"Formation of Cholesterol Bilayer Domains Precedes Formation of Cholesterol Crystals in Membranes Made of the Major Phospholipids of Human Eye Lens Fiber Cell Plasma Membranes","volume":"45","author":"Mainali","year":"2020","journal-title":"Curr. Eye Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8994","DOI":"10.1021\/jp402394m","article-title":"Formation of Cholesterol Bilayer Domains Precedes Formation of Cholesterol Crystals in Cholesterol\/Dimyristoylphosphatidylcholine Membranes: EPR and DSC Studies","volume":"117","author":"Mainali","year":"2013","journal-title":"J. Phys. Chem. B"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.bpj.2011.07.014","article-title":"Phase-Separation and Domain-Formation in Cholesterol-Sphingomyelin Mixture: Pulse-EPR Oxygen Probing","volume":"101","author":"Mainali","year":"2011","journal-title":"Biophys. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00232-011-9412-4","article-title":"Functions of Cholesterol and the Cholesterol Bilayer Domain Specific to the Fiber-Cell Plasma Membrane of the Eye Lens","volume":"245","author":"Subczynski","year":"2012","journal-title":"J. Membr. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2016.03.033","article-title":"Membrane Insertion of \u03b1A-Crystallin Is Oligomer-Size Dependent","volume":"473","author":"Tjondro","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.chemphyslip.2011.08.001","article-title":"Using Spin-Label Electron Paramagnetic Resonance (EPR) to Discriminate and Characterize the Cholesterol Bilayer Domain","volume":"164","author":"Raguz","year":"2011","journal-title":"Chem. Phys. Lipids"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev.biophys.32.110601.142439","article-title":"The State of Lipid Rafts: From Model Membranes to Cells","volume":"32","author":"Edidin","year":"2003","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S0959-440X(02)00351-2","article-title":"Insights into Lipid Raft Structure and Formation from Experiments in Model Membranes","volume":"12","author":"London","year":"2002","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1146\/annurev.biophys.32.110601.141803","article-title":"Model Systems, Lipid Rafts, and Cell Membranes","volume":"33","author":"Simons","year":"2004","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/cbic.201900646","article-title":"Supramolecular Chemistry in the Biomembrane","volume":"21","author":"Nilam","year":"2020","journal-title":"Chembiochem"},{"key":"ref_89","unstructured":"Almeida, P.F.F., Vaz, W.L.C., and Thompson, T.E. (2023, August 23). Lateral Diffusion in the Liquid Phases of Dimyristoylphosphatidylcholine\/Cholesterol Lipid Bilayers: A Free Volume Analysis. Available online: https:\/\/pubs.acs.org\/doi\/epdf\/10.1021\/bi00144a013."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"430","DOI":"10.2478\/s11658-008-0012-y","article-title":"The Liquid-Ordered Phase in Sphingomyelincholesterol Membranes as Detected by the Discrimination by Oxygen Transport (DOT) Method","volume":"13","author":"Wisniewska","year":"2008","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"13573","DOI":"10.1074\/jbc.M010077200","article-title":"Evidence for Distinct Cholesterol Domains in Fiber Cell Membranes from Cataractous Human Lenses","volume":"276","author":"Jacob","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Widomska, J., and Subczynski, W.K. (2019). Why Is Very High Cholesterol Content Beneficial for the Eye Lens but Negative for Other Organs?. Nutrients, 11.","DOI":"10.3390\/nu11051083"},{"key":"ref_93","unstructured":"Thermo Scientific (2022, June 15). BL21(DE3) Competent Cells User Guide (Pub. No. MAN0018595, Rev. A.0) [User Manual]. Available online: https:\/\/www.thermofisher.com\/document-connect\/document-connect.html?url=https:\/\/assets.thermofisher.com\/TFS-Assets%2FLSG%2Fmanuals%2FMAN0018595_BL21_DE3competent_cells_UG.pdf."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0076-6879(98)90032-5","article-title":"Lens \u03b1-Crystallin: Chaperone-like Properties","volume":"Volume 290","author":"Horwitz","year":"1998","journal-title":"Methods in Enzymology"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Walker, J.M. (2005). The Proteomics Protocols Handbook, Humana Press.","DOI":"10.1385\/1592598900"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.bbalip.2008.04.002","article-title":"Human Lens Lipids Differ Markedly from Those of Commonly Used Experimental Animals","volume":"1781","author":"Deeley","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0005-2736(86)90124-0","article-title":"Spin-Label Studies on Phosphatidylcholine-Cholesterol Membranes: Effects of Alkyl Chain Length and Unsaturation in the Fluid Phase","volume":"854","author":"Kusumi","year":"1986","journal-title":"Biochim. Biophys. Acta"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1923\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:55:11Z","timestamp":1760104511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,5]]},"references-count":97,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25031923"],"URL":"https:\/\/doi.org\/10.3390\/ijms25031923","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,5]]}}}