Temperature-Induced Transitions in the Structure and Interfacial Rheology of Human Meibum

Abstract

Meibomian lipids are the primary component of the lipid layer of the tear film. Composed primarily of a mixture of lipids, meibum exhibits a range of melt temperatures. Compositional changes that occur with disease may alter the temperature at which meibum melts. Here we explore how the mechanical properties and structure of meibum from healthy subjects depend on temperature. Interfacial films of meibum were highly viscoelastic at 17°C, but as the films were heated to 30°C the surface moduli decreased by more than two orders of magnitude. Brewster angle microscopy revealed the presence of micron-scale inhomogeneities in meibum films at higher temperatures. Crystalline structure was probed by small angle x-ray scattering of bulk meibum, which showed evidence of a majority crystalline structure in all samples with lamellar spacing of 49 Å that melted at 34°C. A minority structure was observed in some samples with d-spacing at 110 Å that persisted up to 40°C. The melting of crystalline phases accompanied by a reduction in interfacial viscosity and elasticity has implications in meibum behavior in the tear film. If the melt temperature of meibum was altered significantly from disease-induced compositional changes, the resultant change in viscosity could alter secretion of lipids from meibomian glands, or tear-film stabilization properties of the lipid layer.

A Model for the Tear Film and Ocular Surface Temperature for Partial Blinks

“…Two studies have found that evaporation can be reduced in dry eye (Fujishima et al, 1996; Mori et al, 1997) but these authors point out that their subjects are aqueous deficient dry eyes, and Craig et al (2000) speculate that this may be responsible for the reduced evaporation rate. Leiske et al (2012) and Bron et al (2004) also showed that the temperature dynamics may have an impact on lipid layer dynamics, for example, which have temperature-dependent properties.…”

“…Such models could use different properties for the cornea and aqueous humor, as well as for conjunctiva, stroma, and vitreous humor, that are posterior to the tear film. Furthermore, more complex treatments of the tear film, e.g., with separate lipid and aqueous layers, may add additional insights into tear film and OST dynamics, and the OST may be an important input into the properties of the lipid layer (Leiske et al, 2012). …”

“…A sample of tears combining all of its components is mildly shear thinning (Tiffany, 1991) but weakly elastic (Pandit et al, 1999). Recent measurements by Leiske et al (2010) of meibomian lipids (meibum) alone from various mammals show that meibum may have significant elasticity at room temperature; they went on to show that the elasticity is very small above 32°C (Leiske et al, 2012). The contribution of the lipid layer to the overall rheology and properties of tears at in vivo temperatures is yet to be understood.…”

Four Characteristics and a Model of an Effective Tear Film Lipid Layer (TFLL)

“…However, this value might be reduced if there was bending of the cholesterol side chains. It may be noted that small angle X-ray scattering of bulk human meibum 53 indicates multilamellar structures with a lamellar thickness of 4.9 nm, and multilamellar structures of a similar thickness have been demonstrated in meibum spread on saline. 48 It may also be noted that a small quantity of human meibum spread on saline at 20°C (20 μg over 80 cm 2 ) forms a uniform layer (with included “lakes”) of about 5.2 nm thick.…”

Dynamics and function of the tear film in relation to the blink cycle

“…They may also greatly aid in understanding the function and properties of the lipid layer, as well as testing of multilamellar models of the lipid layer structure (King-Smith et al, 2013a; Leiske et al, 2012b; Rosenfeld et al, 2013). Mathematical models may need to incorporate complex surface rheology of the lipid layer as a result of lipid layer structure (Bhamla et al, 2014; Georgiev et al, 2014), but it is unclear at the time of writing how much of the in vivo elastic properties at room temperature remain at physiological temperatures (Leiske et al, 2012a). …”