{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:26:02Z","timestamp":1791501962597,"version":"4.3.4"},"reference-count":107,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T00:00:00Z","timestamp":1698537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Eye Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EY030067"],"award-info":[{"award-number":["R01 EY030067"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Eye Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103408"],"award-info":[{"award-number":["P20GM103408"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Eye Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM109095"],"award-info":[{"award-number":["P20GM109095"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Eye Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["RRID:SCR_019174"],"award-info":[{"award-number":["RRID:SCR_019174"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health, NIGMS","doi-asserted-by":"publisher","award":["R01 EY030067"],"award-info":[{"award-number":["R01 EY030067"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health, NIGMS","doi-asserted-by":"publisher","award":["P20GM103408"],"award-info":[{"award-number":["P20GM103408"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health, NIGMS","doi-asserted-by":"publisher","award":["P20GM109095"],"award-info":[{"award-number":["P20GM109095"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health, NIGMS","doi-asserted-by":"publisher","award":["RRID:SCR_019174"],"award-info":[{"award-number":["RRID:SCR_019174"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biomolecular Research Center","award":["R01 EY030067"],"award-info":[{"award-number":["R01 EY030067"]}]},{"name":"Biomolecular Research Center","award":["P20GM103408"],"award-info":[{"award-number":["P20GM103408"]}]},{"name":"Biomolecular Research Center","award":["P20GM109095"],"award-info":[{"award-number":["P20GM109095"]}]},{"name":"Biomolecular Research Center","award":["RRID:SCR_019174"],"award-info":[{"award-number":["RRID:SCR_019174"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Highly concentrated lens proteins, mostly \u03b2- and \u03b3-crystallin, are responsible for maintaining the structure and refractivity of the eye lens. However, with aging and cataract formation, \u03b2- and \u03b3-crystallin are associated with the lens membrane or other lens proteins forming high-molecular-weight proteins, which further associate with the lens membrane, leading to light scattering and cataract development. The mechanism by which \u03b2- and \u03b3-crystallin are associated with the lens membrane is unknown. This work aims to study the interaction of \u03b2- and \u03b3-crystallin with the phospholipid membrane with and without cholesterol (Chol) with the overall goal of understanding the role of phospholipid and Chol in \u03b2- and \u03b3-crystallin association with the membrane. Small unilamellar vesicles made of Chol\/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (Chol\/POPC) membranes with varying Chol content were prepared using the rapid solvent exchange method followed by probe tip sonication and then dispensed on freshly cleaved mica disk to prepare a supported lipid membrane. The \u03b2L- and \u03b3-crystallin from the cortex of the bovine lens was used to investigate the time-dependent association of \u03b2L- and \u03b3-crystallin with the membrane by obtaining the topographical images using atomic force microscopy. Our study showed that \u03b2L-crystallin formed semi-transmembrane defects, whereas \u03b3-crystallin formed transmembrane defects on the phospholipid membrane. The size of semi-transmembrane defects increases significantly with incubation time when \u03b2L-crystallin interacts with the membrane. In contrast, no significant increase in transmembrane defect size was observed in the case of \u03b3-crystallin. Our result shows that Chol inhibits the formation of membrane defects when \u03b2L- and \u03b3-crystallin interact with the Chol\/POPC membrane, where the degree of inhibition depends upon the amount of Chol content in the membrane. At a Chol\/POPC mixing ratio of 0.3, membrane defects were observed when both \u03b2L- and \u03b3-crystallin interacted with the membrane. However, at a Chol\/POPC mixing ratio of 1, no association of \u03b3-crystallin with the membrane was observed, which resulted in a defect-free membrane, and the severity of the membrane defect was decreased when \u03b2L-crystallin interacted with the membrane. The semi-transmembrane or transmembrane defects formed by the interaction of \u03b2L- and \u03b3-crystallin on phospholipid membrane might be responsible for light scattering and cataract formation. However, Chol suppressed the formation of such defects in the membrane, likely maintaining lens membrane homeostasis and protecting against cataract formation.<\/jats:p>","DOI":"10.3390\/ijms242115720","type":"journal-article","created":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T05:01:08Z","timestamp":1698555668000},"page":"15720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Interaction of \u03b2L- and \u03b3-Crystallin with Phospholipid Membrane Using Atomic Force Microscopy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2404-3799","authenticated-orcid":false,"given":"Nawal K.","family":"Khadka","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 Program, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Haemmerle","sequence":"additional","affiliation":[{"name":"Department of Physics, 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 Program, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/302415a0","article-title":"Short-Range Order of Crystallin Proteins Accounts for Eye Lens Transparency","volume":"302","author":"Delaye","year":"1983","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.bbagen.2015.06.007","article-title":"Gamma Crystallins of the Human Eye Lens","volume":"1860","author":"Vendra","year":"2016","journal-title":"Biochim. Biophys. Acta BBA-Gen. Subj."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/pro.2229","article-title":"Evolution of Crystallins for a Role in the Vertebrate Eye Lens","volume":"22","author":"Slingsby","year":"2013","journal-title":"Protein Sci. Publ. Protein Soc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1350-9462(98)00030-5","article-title":"Alpha-Crystallin as a Molecular Chaperone","volume":"18","author":"Derham","year":"1999","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.exer.2004.06.011","article-title":"\u03b2-Crystallin Association","volume":"79","author":"Hejtmancik","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pbiomolbio.2014.02.004","article-title":"Lens \u03b2-Crystallins: The Role of Deamidation and Related Modifications in Aging and Cataract","volume":"115","author":"Lampi","year":"2014","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3936","DOI":"10.1016\/j.febslet.2007.07.022","article-title":"Protein\u2013Protein Interactions among Human Lens Acidic and Basic \u03b2-Crystallins","volume":"581","author":"Liu","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1432-1033.1993.tb17765.x","article-title":"1h-Nmr Spectroscopy of Bovine Lens Beta-Crystallin. the Role of the Beta B2-Crystallin c-Terminal Extension in Aggregation","volume":"213","author":"Cooper","year":"1993","journal-title":"Eur. J. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15674","DOI":"10.18632\/aging.203147","article-title":"Physiological and Pathological Functions of \u03b2B2-Crystallins in Multiple Organs: A Systematic Review","volume":"13","author":"Li","year":"2021","journal-title":"Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.exer.2012.06.005","article-title":"Electron Tomography of Fiber Cell Cytoplasm and Dense Cores of Multilamellar Bodies from Human Age-Related Nuclear Cataracts","volume":"101","author":"Costello","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1167\/iovs.06-0480","article-title":"Predicted Light Scattering from Particles Observed in Human Age-Related Nuclear Cataracts Using Mie Scattering Theory","volume":"48","author":"Costello","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","first-page":"572","article-title":"Mie Light Scattering Calculations for an Indian Age-Related Nuclear Cataract with a High Density of Multilamellar Bodies","volume":"14","author":"Gilliland","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_13","first-page":"120","article-title":"Multilamellar Bodies as Potential Scattering Particles in Human Age-Related Nuclear Cataracts","volume":"7","author":"Gilliland","year":"2001","journal-title":"Mol. Vis."},{"key":"ref_14","first-page":"1911","article-title":"Cataract as a Protein Condensation Disease: The Proctor Lecture","volume":"38","author":"Benedek","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","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"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1126\/science.377484","article-title":"An Extrinsic Membrane Polypeptide Associated with High-Molecular-Weight Protein Aggregates in Human Cataract","volume":"204","author":"Spector","year":"1979","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0014-4835(05)80012-0","article-title":"Protein Associated with Human Lens \u2018Native\u2019 Membrane during Aging and Cataract Formation","volume":"60","author":"Chandrasekher","year":"1995","journal-title":"Exp. Eye Res."},{"key":"ref_18","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_19","first-page":"177","article-title":"Interaction of Crystallins with the Cytoskeletal-Plasma Membrane Complex of the Bovine Lens","volume":"106","author":"Bloemendal","year":"1984","journal-title":"Ciba Found. Symp."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4786","DOI":"10.1167\/iovs.09-3588","article-title":"Membrane Association of Proteins in the Aging Human Lens: Profound Changes Take Place in the Fifth Decade of Life","volume":"50","author":"Friedrich","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s11357-010-9198-9","article-title":"Tight Binding of Proteins to Membranes from Older Human Cells","volume":"33","author":"Truscott","year":"2011","journal-title":"Age"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5162","DOI":"10.1167\/iovs.09-4947","article-title":"\u03b1- and \u03b2-Crystallins Modulate the Head Group Order of Human Lens Membranes during Aging","volume":"51","author":"Zhu","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","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_24","first-page":"476","article-title":"Crystallins in Water Soluble-High Molecular Weight Protein Fractions and Water Insoluble Protein Fractions in Aging and Cataractous Human Lenses","volume":"10","author":"Harrington","year":"2004","journal-title":"Mol. Vis."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/978-3-030-28151-9_14","article-title":"Crystallins and Their Complexes","volume":"93","author":"Ghosh","year":"2019","journal-title":"Subcell. Biochem."},{"key":"ref_27","first-page":"130","article-title":"The Search for a Solution to Senile Cataracts. Proctor Lecture","volume":"25","author":"Spector","year":"1984","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0014-4835(84)90126-X","article-title":"Characterization of Lens Proteins. IV. Analysis of Soluble High Molecular Weight Protein Aggregates in Human Lenses","volume":"38","author":"Fu","year":"1984","journal-title":"Exp. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1006\/exer.1998.0482","article-title":"Age-Related Changes in Human Lens Crystallins Identified by HPLC and Mass Spectrometry","volume":"67","author":"Ma","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_31","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_32","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_33","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1111\/j.1474-9726.2007.00342.x","article-title":"Presbyopia and Heat: Changes Associated with Aging of the Human Lens Suggest a Functional Role for the Small Heat Shock Protein, Alpha-Crystallin, in Maintaining Lens Flexibility","volume":"6","author":"Heys","year":"2007","journal-title":"Aging Cell"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","unstructured":"Khadka, N.K., Timsina, R., and Mainali, L. (2022). An AFM Approach Applied in a Study of \u03b1-Crystallin Membrane Association: New Insights into Lens Hardening and Presbyopia Development. Membranes, 12.","DOI":"10.3390\/membranes12050522"},{"key":"ref_36","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_37","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_38","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_39","doi-asserted-by":"crossref","unstructured":"Timsina, R., Wellisch, S., Haemmerle, D., and Mainali, L. (2022). Binding of Alpha-Crystallin to Cortical and Nuclear Lens Lipid Membranes Derived from a Single Lens. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911295"},{"key":"ref_40","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_41","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_42","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3109\/02713689408995781","article-title":"On the Interaction of Alpha-Crystallin with Membranes","volume":"13","author":"Zhang","year":"1994","journal-title":"Curr. Eye Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/j.1432-1033.1985.tb09253.x","article-title":"Interaction of Alpha-Crystallin with Lens Plasma Membranes. Affinity for MP26","volume":"152","author":"Mulders","year":"1985","journal-title":"Eur. J. Biochem."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/0014-4835(91)90054-I","article-title":"Interaction of Lens Crystallins with Lipid Vesicles","volume":"52","author":"Ifeanyi","year":"1991","journal-title":"Exp. Eye Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hazen, P., Trossi-Torres, G., Khadka, N.K., Timsina, R., and Mainali, L. (2023). Binding of \u03b2L-Crystallin with Models of Animal and Human Eye Lens-Lipid Membrane. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713600"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1167\/iovs.03-0708","article-title":"\u03b3E-Crystallin Recruitment to the Plasma Membrane by Specific Interaction between Lens MIP\/Aquaporin-0 and \u03b3E-Crystallin","volume":"45","author":"Fan","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_48","first-page":"76","article-title":"Specific Interaction between Lens MIP\/Aquaporin-0 and Two Members of the Gamma-Crystallin Family","volume":"11","author":"Fan","year":"2005","journal-title":"Mol. Vis."},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1006\/exer.1998.0549","article-title":"An Impediment to Glutathione Diffusion in Older Normal Human Lenses: A Possible Precondition for Nuclear Cataract","volume":"67","author":"Sweeney","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.exer.2016.03.004","article-title":"Organization of of Lipids in Fiber-Cell Plasma Membranes of the Eye Lens","volume":"156","author":"Subczynski","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.exer.2004.12.014","article-title":"Alpha-Crystallin Binding in Vitro to Lipids from Clear Human Lenses","volume":"81","author":"Grami","year":"2005","journal-title":"Exp Eye Res"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1194\/jlr.M007716","article-title":"Sphingolipid Distribution Changes with Age in the Human Lens","volume":"51","author":"Deeley","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_54","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-Biomembr."},{"key":"ref_55","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_56","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-Mol. Cell Biol. Lipids"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0022-2275(20)34347-9","article-title":"Membrane Cholesterol and Phospholipid in Consecutive Concentric Sections of Human Lenses","volume":"26","author":"Li","year":"1985","journal-title":"J. Lipid Res."},{"key":"ref_58","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 BBA-Lipids Lipid Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1016\/j.bbamem.2009.09.005","article-title":"Physical Properties of the Lipid Bilayer Membrane Made of Cortical and Nuclear Bovine Lens Lipids: EPR Spin-Labeling Studies","volume":"1788","author":"Raguz","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_60","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\u201370-Year-Old Human Donors","volume":"44","author":"Mainali","year":"2015","journal-title":"Eur. Biophys. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"109131","DOI":"10.1016\/j.exer.2022.109131","article-title":"Membrane Elasticity Modulated by Cholesterol in Model of Porcine Eye Lens-Lipid Membrane","volume":"220","author":"Khadka","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Khadka, N.K., Timsina, R., Rowe, E., O\u2019Dell, M., and Mainali, L. (2021). Mechanical Properties of the High Cholesterol-Containing Membrane: An AFM Study. Biochim. Biophys. Acta BBA-Biomembr., 1863.","DOI":"10.1016\/j.bbamem.2021.183625"},{"key":"ref_63","unstructured":"Grosas, A.B., and Carver, J.A. (2021). Long-Lived Proteins in Human Aging and Disease, John Wiley & Sons, Ltd."},{"key":"ref_64","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_65","first-page":"1609","article-title":"Aggregation in Aqueous Solutions of Bovine Lens Gamma-Crystallins: Special Role of Gamma(s)","volume":"39","author":"Liu","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1006\/exer.1997.0368","article-title":"Towards a Molecular Understanding of Phase Separation in the Lens: A Comparison of the X-Ray Structures of Two HighTc\u03b3-Crystallins, \u03b3E and \u03b3F, with Two LowTc\u03b3-Crystallins, \u03b3B and \u03b3D","volume":"65","author":"Norledge","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.bbamem.2011.10.023","article-title":"Saturation with Cholesterol Increases Vertical Order and Smoothes the Surface of the Phosphatidylcholine Bilayer: A Molecular Simulation Study","volume":"1818","author":"Plesnar","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.bpj.2013.01.021","article-title":"The Nanomechanical Properties of Lipid Membranes Are Significantly Influenced by the Presence of Ethanol","volume":"104","author":"Stetter","year":"2013","journal-title":"Biophys. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5058","DOI":"10.1021\/acs.jpcb.7b02772","article-title":"Membrane Disruption Mechanism of a Prion Peptide (106-126) Investigated by Atomic Force Microscopy, Raman and Electron Paramagnetic Resonance Spectroscopy","volume":"121","author":"Pan","year":"2017","journal-title":"J. Phys. Chem. B"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1110\/ps.0225503","article-title":"In Vitro Unfolding, Refolding, and Polymerization of Human \u03b3D Crystallin, a Protein Involved in Cataract Formation","volume":"12","author":"King","year":"2003","journal-title":"Protein Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.exer.2010.02.007","article-title":"Aggregation of Deamidated Human \u03b2B2-Crystallin and Incomplete Rescue by \u03b1-Crystallin Chaperone","volume":"90","author":"Michiel","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_72","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_73","doi-asserted-by":"crossref","unstructured":"Perissinotto, F., Rondelli, V., Parisse, P., Tormena, N., Zunino, A., Alm\u00e1sy, L., Merkel, D.G., Botty\u00e1n, L., Sajti, S.Z., and Casalis, L. (2019). GM1 Ganglioside Role in the Interaction of Alpha-Synuclein with Lipid Membranes: Morphology and Structure. Biophys. Chem., 255.","DOI":"10.1016\/j.bpc.2019.106272"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9586","DOI":"10.1021\/acsomega.8b01462","article-title":"Lipid Extraction by Alpha-Synuclein Generates Semi-Transmembrane Defects and Lipoprotein Nanoparticles","volume":"3","author":"Pan","year":"2018","journal-title":"ACS Omega"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.bbamem.2012.08.006","article-title":"Transmembrane Pore Formation by the Carboxyl Terminus of Bax Protein","volume":"1828","author":"Garg","year":"2013","journal-title":"Biochim. Biophys. Acta BBA-Biomembr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1073\/pnas.0710625105","article-title":"Mechanism and Kinetics of Pore Formation in Membranes by Water-Soluble Amphipathic Peptides","volume":"105","author":"Lee","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.surfrep.2006.06.001","article-title":"Solid Supported Lipid Bilayers: From Biophysical Studies to Sensor Design","volume":"61","author":"Castellana","year":"2006","journal-title":"Surf. Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.bbamem.2017.01.026","article-title":"Modulation of Lipid Membrane Structural and Mechanical Properties by a Peptidomimetic Derived from Reduced Amide Scaffold","volume":"1859","author":"Khadka","year":"2017","journal-title":"Biochim. Biophys. Acta-Biomembr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1073\/pnas.78.3.1892","article-title":"Biochemical Evidence for Membrane Disintegration in Human Cataracts","volume":"78","author":"Garner","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fnagi.2018.00226","article-title":"Effect of Cholesterol on Membrane Fluidity and Association of A\u03b2 Oligomers and Subsequent Neuronal Damage: A Double-Edged Sword","volume":"10","author":"Peters","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1021\/bi950414i","article-title":"Influence of Cholesterol on the Association of Plasma Proteins with Liposomes","volume":"35","author":"Semple","year":"1996","journal-title":"Biochemistry"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0014-4835(88)80027-7","article-title":"Evolutionary and Functional Relationships between the Basic and Acidic Beta-Crystallins","volume":"46","author":"Slingsby","year":"1988","journal-title":"Exp. Eye Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S1350-9462(98)00027-5","article-title":"Probing the Structure and Interactions of Crystallin Proteins by NMR Spectroscopy","volume":"18","author":"Carver","year":"1999","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"11390","DOI":"10.1021\/acs.jpcb.8b07368","article-title":"Effect of Surfactants on Surface-Induced Denaturation of Proteins: Evidence of an Orientation-Dependent Mechanism","volume":"122","author":"Arsiccio","year":"2018","journal-title":"J. Phys. Chem. B"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e42747","DOI":"10.7554\/eLife.42747","article-title":"Protein Denaturation at the Air-Water Interface and How to Prevent It","volume":"8","author":"Floris","year":"2019","journal-title":"eLife"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.xphs.2022.10.009","article-title":"Surface-Induced Protein Aggregation and Particle Formation in Biologics: Current Understanding of Mechanisms, Detection and Mitigation Strategies","volume":"112","author":"Kopp","year":"2023","journal-title":"J. Pharm. Sci."},{"key":"ref_87","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_88","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1098\/rstb.2010.0302","article-title":"Biological Glass: Structural Determinants of Eye Lens Transparency","volume":"366","author":"Bassnett","year":"2011","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_89","first-page":"703","article-title":"Studies on the Distribution of Cholesterol, Phospholipid, and Protein in the Human and Bovine Lens","volume":"6","author":"Borchman","year":"1989","journal-title":"Lens Eye Toxic. Res."},{"key":"ref_90","first-page":"2798","article-title":"Understanding the \u03b1-Crystallin Cell Membrane Conjunction","volume":"17","author":"Su","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0014-4835(03)00026-5","article-title":"Light Scattering of Human Lens Vesicles in Vitro","volume":"76","author":"Tang","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1167\/iovs.02-0345","article-title":"Influence of Age, Diabetes, and Cataract on Calcium, Lipid-Calcium, and Protein-Calcium Relationships in Human Lenses","volume":"44","author":"Tang","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0014-4835(03)00065-4","article-title":"Changes in the Refractive Index of Lens Fibre Membranes during Maturation\u2014Impact on Lens Transparency","volume":"77","author":"Michael","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0006-3495(79)85237-6","article-title":"Light Scattering of Normal Human Lens I. Application of Random Density and Orientation Fluctuation Theory","volume":"26","author":"Bettelheim","year":"1979","journal-title":"Biophys. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1006\/exer.1997.0467","article-title":"Influence of Cholesterol on the Interaction of \u03b1-Crystallin with Phospholipids","volume":"66","author":"Tang","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5492","DOI":"10.1364\/AO.32.005492","article-title":"Comparison of Surface and Bulk Scattering in Optical Multilayers","volume":"32","author":"Amra","year":"1993","journal-title":"Appl. Opt."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.legalmed.2015.09.002","article-title":"Morphological and Histological Changes in Eye Lens: Possible Application for Estimating Postmortem Interval","volume":"17","author":"Luna","year":"2015","journal-title":"Leg. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0076-6879(98)90032-5","article-title":"[30] Lens \u03b1-Crystallin: Chaperone-like Properties","volume":"Volume 290","author":"Horwitz","year":"1998","journal-title":"Methods in Enzymology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/bip.20630","article-title":"Differential Recognition of Natural and Nonnatural Substrate by Molecular Chaperone Alpha-Crystallin-A Subunit Exchange Study","volume":"85","author":"Biswas","year":"2007","journal-title":"Biopolymers"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"42648","DOI":"10.1074\/jbc.M404444200","article-title":"Role of ATP on the Interaction of Alpha-Crystallin with Its Substrates and Its Implications for the Molecular Chaperone Function","volume":"279","author":"Biswas","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Walker, J.M. (2005). The Proteomics Protocols Handbook, Humana Press. Springer Protocols Handbooks.","DOI":"10.1385\/1592598900"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"14504","DOI":"10.1039\/D0NR03642K","article-title":"Impact of Water on the Lubricating Properties of Hexadecane at the Nanoscale","volume":"12","author":"Cafolla","year":"2020","journal-title":"Nanoscale"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"6522","DOI":"10.1021\/la990371x","article-title":"Organic and Inorganic Contamination on Commercial AFM Cantilevers","volume":"15","author":"Lo","year":"1999","journal-title":"Langmuir"},{"key":"ref_104","first-page":"54924","article-title":"Sub-Nanometer Resolution Imaging with Amplitude-Modulation Atomic Force Microscopy in Liquid","volume":"118","author":"Miller","year":"2016","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1016\/S0006-3495(01)76266-2","article-title":"From Images to Interactions: High-Resolution Phase Imaging in Tapping-Mode Atomic Force Microscopy","volume":"80","author":"Stark","year":"2001","journal-title":"Biophys. J."},{"key":"ref_106","unstructured":"Bloemendal, H. (1981). Molecular and Cellular Biology of the Eye Lens, Wiley-Interscience."},{"key":"ref_107","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."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15720\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:13:39Z","timestamp":1760130819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15720"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,29]]},"references-count":107,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242115720"],"URL":"https:\/\/doi.org\/10.3390\/ijms242115720","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,29]]}}}