Mucin-Like Glycoproteins Modulate Interfacial Properties of a Mimetic Ocular Epithelial Surface

被引:13
|
作者
Liu, Chunzi [1 ]
Madl, Amy C. [1 ]
Cirera-Salinas, Daniel [2 ]
Kress, Wolfgang [2 ]
Straube, Frank [2 ]
Myung, David [1 ,3 ]
Fuller, Gerald G. [1 ]
机构
[1] Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA
[2] Novartis Pharmaceut, Global Drug Dev, Biopharmaceut Proc & Prod Dev, CH-4002 Basel, AG, Switzerland
[3] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
contact angle hysteresis; dry eye disease; interfacial properties; lubricin; muco-adhesion; ocular surfaces; HUMAN CORNEAL-LIMBAL; BOUNDARY LUBRICATION; EXPRESSION; LUBRICIN; BOVINE;
D O I
10.1002/advs.202100841
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Dry eye disease (DED) has high personal and societal costs, but its pathology remains elusive due to intertwined biophysical and biochemical processes at the ocular surface. Specifically, mucin deficiency is reported in a subset of DED patients, but its effects on ocular interfacial properties remain unclear. Herein a novel in vitro mucin-deficient mimetic ocular surface (Mu-DeMOS) with a controllable amount of membrane-tethered mucin molecules is developed to represent the diseased ocular surfaces. Contact angle goniometry on mimetic ocular surfaces reveals that high surface roughness, but not the presence of hydrophilic mucin molecules, delivers constant hydration over native ocular surface epithelia. Live-cell rheometry confirms that the presence of mucin-like glycoproteins on ocular epithelial cells reduces shear adhesive strength at cellular interfaces. Together, optimal surface roughness and surface chemistry facilitate sustainable lubrication for healthy ocular surfaces, while an imbalance between them contributes to lubrication-related dysfunction at diseased ocular epithelial surfaces. Furthermore, the restoration of low adhesive strength at Mu-DeMOS interfaces through a mucin-like glycoprotein, recombinant human lubricin, suggests that increased frictional damage at mucin-deficient cellular surfaces may be reversible. More broadly, these results demonstrate that Mu-DeMOS is a promising platform for drug screening assays and fundamental studies on ocular physiology.
引用
收藏
页数:10
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