Date Published: March 20, 2014
Publisher: Public Library of Science
Author(s): Alicja Wizert, D. Robert Iskander, Lukasz Cwiklik, Danilo Roccatano.
Biophysical properties of the tear film lipid layer are studied at the molecular level employing coarse grain molecular dynamics (MD) simulations with a realistic model of the human tear film. In this model, polar lipids are chosen to reflect the current knowledge on the lipidome of the tear film whereas typical Meibomian-origin lipids are included in the thick non-polar lipids subphase. Simulation conditions mimic those experienced by the real human tear film during blinks. Namely, thermodynamic equilibrium simulations at different lateral compressions are performed to model varying surface pressure, and the dynamics of the system during a blink is studied by non-equilibrium MD simulations. Polar lipids separate their non-polar counterparts from water by forming a monomolecular layer whereas the non-polar molecules establish a thick outermost lipid layer. Under lateral compression, the polar layer undulates and a sorting of polar lipids occurs. Moreover, formation of three-dimensional aggregates of polar lipids in both non-polar and water subphases is observed. We suggest that these three-dimensional structures are abundant under dynamic conditions caused by the action of eye lids and that they act as reservoirs of polar lipids, thus increasing stability of the tear film.
Tear film is important to the health and optics of the human eye , . It refreshes with every blink, undergoes several phases of its kinetics, and eventually ruptures if blinking is suppressed . Tear film instabilities lead to symptoms known as dry eye syndrome, one of the commonly reported eye ailments . When untreated, it can lead to blindness. Dry eye is significantly more common in females than males and it is highly prevalent in contact lens wearers –.
The simulated systems contained water, polar lipids, and non-polar lipids. The lipid composition employed mimics the experimentally assessed lipidome of the tear film, as discussed in the Introduction. More specifically, the choice of polar lipids and their concentrations directly reflect the current knowledge about lipidome of the aqueous tear fluid , whereas two experimentally most abundant non-polar lipids were selected here to model the non-polar lipid layer . The previous computational studies of tear film aimed at explaining the role of the polar to non-polar lipids ratio for the tear film stability , . Systems with a relatively thin, about monomolecular, layer of polar lipids directly covering the water phase, and with only a minor component of non-polar lipids deposited on the polar layer were considered therein. Based on experimental studies, the non-polar sub-layer present in the TFLL is expected to be substantially thicker than the polar one, with the estimated thickness of up to 90 nm , . Hence, to capture essential features of the whole TFLL, we considered systems with abundance of non-polar lipids. As it will be demonstrated, this approach allowed us to obtain a relatively stable multi-layered lipid system which can be considered as a plausible model of the tear film.
Simulations were performed at different lateral compressions to mimic varying surface pressure conditions expected during an eye blink . To characterize the compression, we utilize the area per polar lipid (APPL) parameter defined as the lateral area of the simulation box per number of all polar lipids in one monolayer. First, equilibrium MD simulations, employing the canonical ensemble were performed so that the APPL was kept constant during each simulation. The values of APPL between 31.5 and 71 Å2 were applied in these simulations. As will be discussed in the following, two different types of behavior were observed with varying lateral compression. For low lateral compressions characterized by APPL > 60 Å2, the water-lipid interface was approximately planar, while for more compressed systems, at APPL ≤ 60 Å2, undulations of the lipid-water interface were observed. Additionally, non-equilibrium simulations were performed in which the system was laterally compressed either beyond or just before the collapse point of the lipid film and then laterally decompressed. In those simulations buckling and interface undulations occurred followed by a reorganization of the lipid film and formation of various three-dimensional structures.
The main aim was to study at the molecular level biophysical properties of a realistic tear film model under conditions mimicking those experienced by the tear film under physiological conditions. Molecular-level organization of lipid tear film was studied employing coarse grain molecular dynamics simulations. The lipid composition used here directly reflects the lipidome of the aqueous tear fluid . This lipidome is still of qualitative nature and that further studies are required to arrive at a fully quantitative result. Our model also includes a relatively large amount of non-polar lipids, simulating those of the Meibomian glad origin, which are experimentally known to be the dominant component of the lipid tear film and which are shown here to have a crucial role in modulating lipid film behavior. In real eye, such a clear distinction between aqueous tear lipids and meibomian glad lipids may not necessarily be the case. As pointed out in the recent study by Borchman et al., the meibum may also be a source of tear lipids . It is also worth noting that lipid-protein interactions are supposed to play an important role in the tear film. However, this issue was beyond the scope of the current study.