King-Smith P Ewen, Begley Carolyn G, Braun Richard J
Ohio State University, Columbus, OH, USA.
Indiana University, Bloomington, IN, USA.
Ocul Surf. 2025 Aug 21;38:251-259. doi: 10.1016/j.jtos.2025.08.006.
Two models of meibum and the TFLL are proposed. The first model is based on a reanalysis of x-ray studies which show the predominance of 11 nm thick lamellae above 30 °C, but below 30 °C, 5 nm thick lamellae predominate. By analogy to skin lipid, we denote these the long (LPP) and short period phase (SPP), respectively. In the model, the SPP lamellae are interdigitated bilayers of cholesteryl esters (CEs) oriented towards one surface and wax esters (WEs) oriented towards the other surface, with the long interdigitated CE and WE chains tilted. These lamellae are stacked with the same polarity, e.g., CE surface uppermost. At ocular surface temperature, the polarity of alternate layers is reversed, forming the LPP. This doubles the periodicity, but the tilt of the LPP long chains is reduced to render the periodicity more than twice the SPP. The model is consistent with changes in meibum near 30 °C found in calorimetry, viscoelasticity, infrared spectra, birefringence, reflectance, and high resolution images of meibum spread on saline. A secondary model explains the finding that most long saturated chains in CEs and WEs are branched. We propose a 'bump and hollow' model where a 'bump' is a branch on a WE chain fitting into a 'hollow', the linking oxygen atom in a neighboring CE chain; likewise, a bump on a CE chain fits a hollow on a WE chain. We aim to stimulate further development of lipid layer models, including the role of other molecules, to aid understanding of dry eye disease (DED).