Tear Film Stability as a Function of Tunable Mucin Concentration Attached to Supported Lipid Bilayers

Cui, Kiara; Myung, David; Fuller, Gerald G.

doi:10.1021/acs.jpcb.2c04154

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…The base DOPC lipid is always in large excess, and we assume that the minority lipid in SLB or vesicle does not aggregate significantly; in this case we can assume that the diffusion constants of the lipids are all similar to the base lipid. [ 38 ] Multiple experiments indicate a relative error in the diffusion constant values of 10–20%. A lower diffusion coefficient (approximately half of the value found for the Texas Red lipid) was observed for SAv after anchoring it to the biotin lipid (Figure S6b, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Recruitment of Receptors and Ligands in a Weakly Multivalent System with Omnipresent Signatures of Superselective Binding

Allegri

Huskens

2023

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For instance, virus internalization by cells occurs in specialized regions where the recruitment of receptors takes place. [11] Typically, influenza A viruses infect their host by entering into cells via receptor-mediated endocytosis, [12,13] during which the distribution of corresponding receptors in the cell membrane is rearranged and co-localized, as a direct result of receptor clustering induced by weak and multiple ligand-receptor interactions. Thus, gaining understanding of the mechanism of receptor clustering induced by weakly multivalent interactions is essential in order to understand its effect in virus infection at the molecular level, and also to allow its application as a design rule in artificial self-assembling systems.In most natural biological systems, multivalent interactions are composed of many, but individually weakly binding, interaction pairs, which contributes to the dynamic character of the interactions. [14][15][16][17][18] We can relate this behavior to the fact that the overall affinity (K ov ) can be orders of magnitude higher than the individual, monovalent affinity (K i ). More precisely, each additional interaction pair contributes to the overall affinity by only a small enhancement factor, [1,19] which indicates at the same time that each interaction pair is dynamically equilibrating between its bound and unbound states, the frequency of which is dictated by the intrinsic dissociation rate constant. In contrast, as an opposing example of a strongly binding system, the individual affinity of biotin-streptavidin (SAv) is very high, [20,21] and as a result, assemblies based on multiple biotin-SAv interactions are viewed to be practically irreversible. [22][23][24] As an example of the dynamic nature of weak interactions, it has been reported that the low-density lipoprotein (LDL) receptors in the cell membrane will return to the cell membrane surface after the receptor-mediated endocytosis of a virus particle, where they again cluster in coated pits, [25,26] indicating that the LDL receptors still keep their mobility and are recycled in the recruitment process. This recycling property accounts for the fact that the receptors during clustering are still dynamic at their binding sites, allowing switching between the diffusive and the clustering states.To provide quantitative insight into these molecular processes, it is necessary to build synthetic model systems that Recruitment of receptors at membrane interfaces is essential in biological recognition and uptake processes. The interactions that induce recruitment are typically weak at the level of individual interaction pairs, but are strong and selective at the level of recruited ensembles. Here, a model system is demonstrated, based on the supported lipid bilayer (SLB) that mimics the recruitment process induced by weakly multivalent interactions. The weak (mm range) histidine-nickel-nitrilotriacetate (His 2 -NiNTA) pair is employed owing to its ease of implementation in both synthetic and biological systems. The recruitment of rece...

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Section: Resultsmentioning

confidence: 99%

Recruitment of Receptors and Ligands in a Weakly Multivalent System with Omnipresent Signatures of Superselective Binding

Allegri

Huskens

2023

Small

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“…Based on biophysical, cell/organ culture, and observational evidence, MAMs have been proposed to play critical roles at the ocular surface in tear film stability 7 , 11 , transcellular barrier function 20 , 21 , apical epithelial cell architecture 21 , dry eye pathology 14 and dampening of the immune response 27 . Here we investigated these hypotheses by evaluating the phenotype of transgenic Muc4 KO mice.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence from biophysical modeling and cell culture studies suggests that both secreted mucins and MAMs contribute to tear film stability and spreading by providing shear thinning properties to tears, reducing friction during blinks, and enhancing corneal wettability wettability 7 , 11 , 12 . Instability of the tear film results in dry eye, a common affliction that affects 5% to 34% of people globally 13 .…”

Section: Introductionmentioning

confidence: 99%

Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model

Martinez-Carrasco,

Rachagani,

Batra

et al. 2023

Sci Rep

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Membrane-associated mucins (MAMs) are proposed to play critical roles at the ocular surface; however, in vivo evidence has been lacking. Here we investigate these roles by phenotyping of a Muc4 KO mouse. Histochemical analysis for expression of the beta-galactosidase transgene replacing Muc4 revealed a spiraling ribbon pattern across the corneal epithelium, consistent with centripetal cell migration from the limbus. Depletion of Muc4 compromised transcellular barrier function, as evidenced by an increase in rose bengal staining. In addition, the corneal surface was less smooth, consistent with disruption of tear film stability. While surface cells presented with well-developed microprojections, an increase in the number of cells with fewer microprojections was observed. Moreover, an increase in skin-type keratin K10 and a decrease in transcription factor Pax6 was observed, suggesting an incipient transdifferentiation. Despite this, no evidence of inflammatory dry eye disease was apparent. In addition, Muc4 had no effect on signaling by toll-like receptor Tlr4, unlike reports for MUC1 and MUC16. Results of this study provide the first in vivo evidence for the role of MAMs in transcellular barrier function, tear film stability, apical epithelial cell architecture, and epithelial mucosal differentiation at the ocular surface.

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“…The underlying aqueous tear fluid has a significant impact on lipid layer function, and the spread of the lipid layer may correlate with the amount of tear fluid present in the aqueous compartments of the tear film. The volume of the tear film’s aqueous phase is particularly significant because it contains surfactant-active substances (mucins) that are necessary for the lipid layer to spread and function [ 69 , 70 , 71 , 72 ].…”

Section: Evaporation Contributing Factorsmentioning

confidence: 99%

One Soul and Several Faces of Evaporative Dry Eye Disease

Di Zazzo,

Barabino,

Fasciani

et al. 2024

JCM

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The ocular surface system interacts with, reacts with, and adapts to the daily continuous insults, trauma, and stimuli caused by direct exposure to the atmosphere and environment. Several tissue and para-inflammatory mechanisms interact to guarantee such an ultimate function, hence maintaining its healthy homeostatic equilibrium. Evaporation seriously affects the homeostasis of the system, thereby becoming a critical trigger in the pathogenesis of the vicious cycle of dry eye disease (DED). Tear film lipid composition, distribution, spreading, and efficiency are crucial factors in controlling water evaporation, and are involved in the onset of the hyperosmolar and inflammatory cascades of DED. The structure of tear film lipids, and subsequently the tear film, have a considerable impact on tears’ properties and main functions, leading to a peculiar clinical picture and specific management.

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Tear Film Stability as a Function of Tunable Mucin Concentration Attached to Supported Lipid Bilayers

Cited by 5 publications

References 20 publications

Recruitment of Receptors and Ligands in a Weakly Multivalent System with Omnipresent Signatures of Superselective Binding

Recruitment of Receptors and Ligands in a Weakly Multivalent System with Omnipresent Signatures of Superselective Binding

Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model

One Soul and Several Faces of Evaporative Dry Eye Disease

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