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Lukasz Cwiklik, Adéla Melcrová, Philippe Daull, Jean-Sebastien Garrigue; Tear Film Break-Up: a molecular level view by employing in silico approach. Invest. Ophthalmol. Vis. Sci. 2017;58(8):472.
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© ARVO (1962-2015); The Authors (2016-present)
Tear film breakup is assumed to be dependent on lipid composition of the tear film lipid layer (TFLL). However, both mechanism of the breakup and the role played by lipids are still not sufficiently known. This issue is particularly important for understanding tear film breakup in the case of dry eye where deficiencies of the TFLL often play a critical role. The macroscopically observed breakup is governed by the underlying molecular-level interactions between individual tear film components. We hypothesize that various lipid classes of TFLL play specific role during the onset of tear film breakup at the molecular level and hence have different role for maintaining tear film stability.
Molecular dynamics in silico simulations of the TFLL model in contact with aqueous subphase were performed. The model includes several types of polar and nonpolar lipids described employing the coarse grain MARTINI model. Microsecond-long simulations of laterally relaxed and compressed TFLL with varying polar lipids composition were performed.
Deficiency of polar lipids in TFLL leads to poration of the polar monolayer and increased water-nonpolar lipids contacts. In contrast to the TFLL rich in polar lipids where cholesteryl esters partially incorporate in the polar monolayer and interact with water, in the deficient TFLL cholesteryl esters avoid interactions with the water subphase. Contacts between nonpolar triglycerides and the water phase are enhanced. In the case of laterally compressed and hence undulated TFLL, the diminished polar lipid content causes flattening of the water-lipid interface to minimize the interfacial tension. As observed in the laterally relaxed TFLL, cholesterol esters avoid contacts with water while triglyceride-water contact become more abundant.
The results obtained via in silico simulations support the hypothesis that involvement of various lipid classes differs during the breakup of the tear film deficient in polar lipids. Polar lipids form an incomplete monolayer with pores present. The pores are predominantly occupied by triglycerides involved in direct contacts with water while the presence of cholesteryl ester at the water-lipid boundary is diminished. Due to unfavorable water-triglyceride contacts, the system tends to reduce water-lipid interface which would lead to its breakdown at the macroscopic level.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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