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Alicja Wizert, D. Robert Iskander, Lukasz Cwiklik; Simulation Study of Proteins Interactions with Tear Film Lipid Layer on the Molecular Level. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3201. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate lysozyme interactions with the tear film lipid layer (TFLL) model and elucidate on the process of the protein penetration into the lipid layer by incorporating computer simulations.
The initial model of tear film (based on our previous work [Wizert et al. PloS One, 9.3 (2014): e92461]) contains 1600 molecules of the most abundant polar (POPC, POPE, SM, Cer) and non-polar (TG,CE) lipid components in a human tear film, about 35000 water molecules and one molecule of lysozyme in either aqueous or lipid phase. State-of-art molecular dynamics (MD) simulations are performed using coarse grained MARTINI force field using dedicated software GROMACS 4.6.1. MD simulations were carried out in the canonical mode to analyze the stability of the proposed model in an equilibrium system at a fixed pressure and temperature. In order to study the lipid film under conditions of lateral squeezing and to account for eye blinks (introduces substantial variations in the lateral pressure), non-equilibrium MD simulations applying lateral pressure were performed.
Previous study has shown that in the scale of nanoseconds the proposed model provides a stable layer both in the relaxed state and under high lateral pressure. However, high compression forces lipid layer to undulate and above the critical surface tension to extrude lipids into nonpolar phase. As a result of the new study we show how a lysozyme molecule interacts with lipid layer and how those interactions modulate upon lateral compression. We show conditions at which the lysozyme molecule can be incorporated into the TFLL and specify its interactions with particular types of TFLL lipids.
The presence of proteins that can interact with lipids in the aqueous phase suggests that protein-lipid interactions that occur in vivo may be an important factor influencing the biophysical properties of tears. Lysozyme, a most abundant protein in the human tear film, has shown to contribute to decreasing surface tension of TFLL thus potentially to stabilize tear film.
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