Molecular-Level Organization of the Tear Film Lipid Layer: A Molecular Dynamics Simulation Study

Abstract

Tear film is essential to the health and optics of the human eye. It refreshes with every blink and ruptures if blinking is suppressed. Its instabilities lead to the dry eye syndrome. The outermost layer of the tear film consists of lipids which provide an optically smooth surface over the cornea and retard water evaporation. The tear film lipid layer formation and structure are still debated. We employ coarse grain molecular dynamics simulations to study molecular-level structure and dynamics of the tear film lipid layer. A novel, realistic tear film model under conditions mimicking those experienced by the tear film under physiological conditions was built and employed.Simulations show that polar phospholipids separate their non-polar counterparts from the water phase, constituting a monomolecular uniform platform at which a thick non-polar lipid layer is formed. This lipid arrangement is stable upon lateral compression. A significant restructuring of the film occurs upon non-equilibrium lateral compression which mimics eye blinks. The water/lipid interface undulates, and lipids are sorted based on their head group size. Undulations of the water/lipid boundary are followed by transfer of some of polar lipids and water toward the non-polar phase, resulting in formation of inverse micelles in the non-polar lipid layer with water encapsulated by polar lipids. Moreover, some of non-polar lipids are transferred into the water phase in vesicles formed by polar lipids.We predict that the tear film lipid layer at the molecular level is a dynamic and non-uniform assembly with lipids and water forming numerous three-dimensional structures in the vicinity of the lipid/water interface. These structures form and reorganize due to the action of eye lids during blinks. They may serve as lipid reservoirs and thus effectively increase stability of the tear film.