Abstract
Purpose :
Nonpolar lipids are the most abundant components of the Tear Film Lipid Layer – the outermost structure of the Tear Film. This complex mixture of various classes of molecules is secreted by Meibomian glands and spread onto the tear-air interface lowering interfacial surface tension and hindering tear evaporation. In TFLL, the nonpolar lipids are accompanied by much less abundant polar lipid species which are responsible for an efficient spreading and stabilization of TFLL at the aqueous tear subphase. As demonstrated by our earlier in silico molecular level models, nonpolar and polar lipids readily and specifically interact to form a stable lipid layer on the Tear Film. These interactions predominantly involve the aliphatic chains of both lipid classes and are modulated by the chain length of involved lipids. Notably, the lengths of tear film lipid tails vary. Furthermore, in some drug formulations, relatively short so-called medium-chain triglycerides are used. We hypothesize that alterations of nonpolar lipids chain length and their saturation change TFLL stability.
Methods :
In silico molecular dynamics simulations employing TFLL model in contact with aqueous subphase were performed. The model included several types of polar and nonpolar lipids. Nonpolar lipids with reduced chain length and different tail saturation were introduced in the nonpolar sublayer of the film. Experiments involving analogous lipid films consisting of synthetic lipid species were performed using Langmuir trough coupled with a fluorescence microscope.
Results :
Nonpolar lipids with the relatively long and unsaturated chains, corresponding to that found under typical physiological conditions, form a well-behaving film at the water-air interface. In particular, they are relatively well separated from the aqueous subphase by a sublayer of polar lipids. A reduction of the chain length and chain saturation leads to an enhanced penetration of the short-chain nonpolar lipids into the polar sublayer and modification of its properties. Corresponding alterations of the lipid film structure were also observed experimentally using synthetic lipid mixtures.
Conclusions :
In silico molecular dynamics simulations of TFLL-mimicking models support the hypothesis that shortening and saturating of nonpolar lipids chains modifies structure and properties of Tear Film Lipid Layer.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.