The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film. We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids. The aim is to better understand the macroscopically observed eye drops-tear film interactions by rationalizing them at the molecular level. To this end, we employ a multi-scale approach combining experiments on human meibomian lipid extracts, measurements using synthetic lipid films, and in silico molecular dynamics simulations. By combining these methods, we demonstrate that the studied compounds specifically interact with the tear lipid film enhancing its structure, surfactant properties, and elasticity. The observed effects are cooperative and can be further modulated by material packing at the tear-air interface.

Department of Cytology and Embryology Faculty of Biology University of Sofia 1504 Sofia Bulgaria

iBB Institute for Bioengineering and Biosciences Complexo Interdisciplinar IST Universidade de Lisboa 1649 004 Lisbon Portugal

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences 16610 Prague Czech Republic

J Heyrovský Institute of Physical Chemistry Czech Academy of Sciences Dolejškova 3 18223 Prague Czech Republic

SANTEN SAS Novagali Innovation Center 1 rue Pierre Fontaine Bâtiment Genavenir 4 CEDEX F 91458 Evry France

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