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.

Institute of Biomedical Engineering and Instrumentation Wroclaw University of Technology Wroclaw Poland

J Heyrovský Institute of Physical Chemistry Academy of Sciences of the Czech Republic v v i Prague Czech Republic; Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic v v i Prague Czech Republic; Department of Physics Tampere University of Technology Tampere Finland

Zobrazit více v PubMed

Rolando M, Zierhut M (2001) The ocular surface and tear film and their dysfunction in dry eye disease. Survey of Ophthalmology 45: S203–S210. PubMed

Tutt R, Bradley A, Begley C, Thibos LN (2000) Optical and visual impact of tear break-up in human eyes. Investigative Ophthalmology & Visual Science 41: 4117–4123. PubMed

Szczesna DH, Iskander DR (2010) Lateral Shearing Interferometry for Analysis of Tear Film Surface Kinetics. Optometry and Vision Science 87: 513–517. PubMed

Bron AJ (2007) Methodologies to diagnose and monitor dry eye disease: Report of the Diagnostic Methodology Subcommittee of the international Dry Eye WorkShop (2007). Ocular Surface 5: 108–152. PubMed

Schaumberg DA, Dana R, Buring JE, Sullivan DA (2009) Prevalence of Dry Eye Disease Among US Men Estimates From the Physicians' Health Studies. Archives of Ophthalmology 127: 763–768. PubMed PMC

Schaumberg DA, Sullivan DA, Buring JE, Dana MR (2003) Prevalence of dry eye syndrome among US women. American Journal of Ophthalmology 136: 318–326. PubMed

Fonn D, Situ P, Simpson T (1999) Hydrogel lens dehydration and subjective comfort and dryness ratings in symptomatic and asymptomatic contact lens wearers. Optometry and Vision Science 76: 700–704. PubMed

Begley CG, Caffery B, Nichols KK, Chalmers R (2000) Responses of contact lens wearers to a dry eye survey. Optometry and Vision Science 77: 40–46. PubMed

Du Toit R, Situ P, Simpson T, Fonn D (2001) The effects of six months of contact lens wear on the tear film, ocular surfaces, and symptoms of presbyopes. Optometry and Vision Science 78: 455–462. PubMed

Holly FJ (1985) Physical-chemistry of the normal and disordered tear film. Transactions of the Ophthalmological Societies of the United Kingdom 104: 374–380. PubMed

Tomlinson A, Khanal S (2005) Assessment of tear film dynamics: Quantification approach. Ocular Surface 3: 81–95. PubMed

Khanal S, Millar TJ (2010) Nanoscale phase dynamics of the normal tear film. Nanomedicine-Nanotechnology Biology and Medicine 6: 707–713. PubMed

Dilly PN (1994) Structure and function of the tear film. Lacrimal Gland, Tear Film, and Dry Eye Syndromes: Basic Science and Clinical Relevance 350: 239–247. PubMed

Tragoulias ST, Anderton PJ, Dennis GR, Miano F, Millar TJ (2005) Surface pressure measurements of human tears and individual tear film components indicate that proteins are major contributors to the surface pressure. Cornea 24: 189–200. PubMed

Holly FJ (1973) Formation and rupture of tear film. Experimental Eye Research 15: 515–525. PubMed

Szczesna-Iskander DH, Iskander DR (2012) Future Directions in Non-Invasive Measurements of Tear Film Surface Kinetics. Optometry and Vision Science 89: 749–759. PubMed

Bron AJ, Tiffany JM, Gouveia SM, Yokoi N, Voon LW (2004) Functional aspects of the tear film lipid layer. Experimental Eye Research 78: 347–360. PubMed

Korb DR, Greiner JV, Glonek T (1996) Tear film lipid layer formation: Implications for contact lens wear. Optometry and Vision Science 73: 189–192. PubMed

Craig JP, Tomlinson A (1997) Importance of the lipid layer in human tear film stability and evaporation. Optometry and Vision Science 74: 8–13. PubMed

King-Smith PE, Nichols JJ, Nichols KK, Fink BA, Braun RJ (2008) Contributions of evaporation and other mechanisms to tear film thinning and break-up. Optometry and Vision Science 85: 623–630. PubMed

King-Smith PE, Fink BA, Nichols JJ, Nichols KK, Braun RJ, et al. (2009) The Contribution of Lipid Layer Movement to Tear Film Thinning and Breakup. Investigative Ophthalmology & Visual Science 50: 2747–2756. PubMed

Rantamaki AH, Javanainen M, Vattulainen I, Holopainen JM (2012) Do Lipids Retard the Evaporation of the Tear Fluid? Investigative Ophthalmology & Visual Science 53: 6442–6447. PubMed

Goto E, Tseng SCG (2003) Differentiation of lipid tear deficiency dry eye by kinetic analysis of tear interference images. Archives of Ophthalmology 121: 173–180. PubMed

Shine WE, McCulley JP (1998) Keratoconjunctivitis sicca associated with meibomian secretion polar lipid abnormality. Archives of Ophthalmology 116: 849–852. PubMed

Glasgow BJ, Marshall G, Gasymov OK, Abduragimov AR, Yusifov TN, et al. (1999) Tear lipocalins: Potential lipid scavengers for the corneal surface. Investigative Ophthalmology & Visual Science 40: 3100–3107. PubMed

Dartt DA (2011) Tear Lipocalin: Structure and Function. Ocular Surface 9: 126–138. PubMed PMC

Glasgow BJ, Gasymov OK, Abduragimov AR, Engle JJ, Casey RC (2010) Tear Lipocalin Captures Exogenous Lipid from Abnormal Corneal Surfaces. Investigative Ophthalmology & Visual Science 51: 1981–1987. PubMed PMC

Jester JV, Nicolaides N, Smith RE (1981) Meibomian gland studies - histologic and ultrastructural investigations. Investigative Ophthalmology & Visual Science 20: 537–547. PubMed

Nicolaides N, Santos EC, Smith RE, Jester JV (1989) Meibomian gland dysfunction 3. Meibomian gland lipids. Investigative Ophthalmology & Visual Science 30: 946–951. PubMed

McCulley JP, Shine WE (2003) Meibomian gland function and the tear lipid layer. Ocul Surf 1: 97–106. PubMed

Butovich IA (2008) On the lipid composition of human meibum and tears: Comparative analysis of nonpolar lipids. Investigative Ophthalmology & Visual Science 49: 3779–3789. PubMed PMC

Rantamaki AH, Seppanen-Laakso T, Oresic M, Jauhiainen M, Holopainen JM (2011) Human tear fluid lipidome: from composition to function. PLoS One 6: e19553. PubMed PMC

Borchman D, Foulks GN, Yappert MC, Tang DX, Ho DV (2007) Spectroscopic evaluation of human tear lipids. Chemistry and Physics of Lipids 147: 87–102. PubMed

Butovich IA (2009) The Meibomian Puzzle: Combining pieces together. Progress in Retinal and Eye Research 28: 483–498. PubMed PMC

Wollensak G, Mur E, Mayr A, Baier G, Gottinger W, et al. (1990) Effective methods for the investigation of human tear film proteins and lipids. Graefes Arch Clin Exp Ophthalmol 228: 78–82. PubMed

Nagyova B, Tiffany JM (1999) Components responsible for the surface tension of human tears. Curr Eye Res 19: 4–11. PubMed

Borchman D, Foulks GN, Yappert MC, Ho DV (2007) Temperature-induced conformational changes in human tearlipids hydrocarbon chains. Biopolymers 87: 124–133. PubMed

Borchman D, Yappert MC, Milliner SE, Smith RJ, Bhola R (2013) Confirmation of the presence of squalene in human eyelid lipid by heteronuclear single quantum correlation spectroscopy. Lipids 48: 1269–1277. PubMed

Svitova TF, Lin MC (2010) Tear Lipids Interfacial Rheology: Effect of Lysozyme and Lens Care Solutions. Optometry and Vision Science 87: 10–20. PubMed PMC

King-Smith PE, Nichols JJ, Braun RJ, Nichols KK (2011) High Resolution Microscopy of the Lipid Layer of the Tear Film. Ocular Surface 9: 197–211. PubMed PMC

Rantamaki A, Telenius J, Koivuniemi A, Vattulainen I, Holopainen JM (2011) Lessons from the biophysics of interfaces: Lung surfactant and tear fluid. Progress in Retinal and Eye Research 30: 204–215. PubMed

Kulovesi P, Telenius J, Koivuniemi A, Brezesinski G, Vattulainen I, et al. (2012) The impact of lipid composition on the stability of the tear fluid lipid layer. Soft Matter 8: 5826–5834.

Telenius J, Koivuniemi A, Kulovesi P, Holopainen JM, Vattulainen I (2012) Role of Neutral Lipids in Tear Fluid Lipid Layer: Coarse-Grained Simulation Study. Langmuir 28: 17092–17100. PubMed

Marrink SJ, de Vries AH, Mark AE (2004) Coarse Grained Model for Semiquantitative Lipid Simulations. The Journal of Physical Chemistry B 108: 750–760.

Baoukina S, Monticelli L, Risselada HJ, Marrink SJ, Tieleman DP (2008) The molecular mechanism of lipid monolayer collapse. Proc Natl Acad Sci U S A 105: 10803–10808. PubMed PMC

Marrink SJ, Tieleman DP (2013) Perspective on the Martini model. Chem Soc Rev 42: 6801–6822. PubMed

Kulovesi P, Telenius J, Koivuniemi A, Brezesinski G, Rantamaki A, et al. (2010) Molecular organization of the tear fluid lipid layer. Biophys J 99: 2559–2567. PubMed PMC

Hess B, Kutzner C, van der Spoel D, Lindahl E (2008) GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. Journal of Chemical Theory and Computation 4: 435–447. PubMed

Marrink SJ, Risselada HJ, Yefimov S, Tieleman DP, de Vries AH (2007) The MARTINI force field: coarse grained model for biomolecular simulations. J Phys Chem B 111: 7812–7824. PubMed

Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. The Journal of Chemical Physics 81: 3684–3690.

Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: A new molecular dynamics method. Journal of Applied Physics 52: 7182–7190.

Shaw AJ, Collins MJ, Davis BA, Carney LG (2009) Eyelid pressure: inferences from corneal topographic changes. Cornea 28: 181–188. PubMed

Kamal MM, Mills D, Grzybek M, Howard J (2009) Measurement of the membrane curvature preference of phospholipids reveals only weak coupling between lipid shape and leaflet curvature. Proceedings of the National Academy of Sciences 106: 22245–22250. PubMed PMC

Perera MN, Lin SH, Peterson YK, Bielawska A, Szulc ZM, et al. (2012) Bax and Bcl-xL exert their regulation on different sites of the ceramide channel. Biochemical Journal 445: 81–91. PubMed

Hu M, Briguglio JJ, Deserno M (2012) Determining the Gaussian Curvature Modulus of Lipid Membranes in Simulations. Biophysical journal 102: 1403–1410. PubMed PMC

Vuorela T, Catte A, Niemela PS, Hall A, Hyvonen MT, et al. (2010) Role of Lipids in Spheroidal High Density Lipoproteins. Plos Computational Biology 6. PubMed PMC

Karaborni S, Siepmann JI (1994) The effects of finite size in molecular dynamics simulations of Langmuir monolayers. Molecular Physics 83: 345–350.

Doane MG (1980) Dynamics of the Human Blink. In: Jaeger W, editor. Plastische Chirurgie der Lider und Chirurgie der Tränenwege: J.F. Bergmann-Verlag. pp. 13–17.

Smaby JM, Brockman HL (1978) Properties of Cholesteryl Oleate and Triolein in Mixed Monolayers at Air - Water Interface. Journal of Lipid Research 19: 325–331. PubMed

Hamilton JA, Oppenheimer N, Cordes EH (1977) C-13 Nuclear Magnetic-Resonance Studies of Cholesteryl Esters and Cholesteryl Ester-Triglyceride Mixtures. Journal of Biological Chemistry 252: 8071–8080. PubMed

Guo W, Hamilton JA (1996) C-13 MAS NMR studies of crystalline cholesterol and lipid mixtures modeling atherosclerotic plaques. Biophysical Journal 71: 2857–2868. PubMed PMC

King-Smith PE, Bailey MD, Braun RJ (2013) Four characteristics and a model of an effective tear film lipid layer (TFLL). Ocul Surf 11: 236–245. PubMed PMC

Doughty MJ (2002) Further Assessment of Gender- and Blink Pattern-Related Differences in the Spontaneous Eyeblink Activity in Primary Gaze in Young Adult Humans. Optometry & Vision Science 79: 439–447. PubMed

Millar TJ (2013) A mechanism to explain the behaviour of spread films of meibomian lipids. Curr Eye Res 38: 220–223. PubMed

The Potential Role of SP-G as Surface Tension Regulator in Tear Film: From Molecular Simulations to Experimental Observations

Improving Stability of Tear Film Lipid Layer via Concerted Action of Two Drug Molecules: A Biophysical View

Cationic Emulsion-Based Artificial Tears as a Mimic of Functional Healthy Tear Film for Restoration of Ocular Surface Homeostasis in Dry Eye Disease