Gel-Forming Mucin Improves Lubricity Across Model Gemini Epithelial Cell Interfaces

The glycocalyx is a glycosylated protein network gel that protects the underlying epithelial cells. Although the glycocalyx is thought to be lubricious, in Gemini contacts with epithelial cells the glycocalyx is found to have high friction (µ ~ 0.20). The model of the tear film is that of a delicate hierarchical multiscale assembly of mucins that form a network aqueous gel interface between the glycocalyces of the conjunctival and corneal epithelial layers to provide lubricity and gentle shearing. The integrity of this aqueous gel is maintained through mucin entanglement, and dynamic flickering bonds of disulfide bridges, Ca²⁺-mediated links, and hydrogen bonding. The tear film has a unique set of rheological properties and behaviors, from a heterogeneous yield stress gel-like fluid at low shear stress to a low-viscosity fluid at high shear rate. In this manuscript, we have demonstrated that the gel-forming mucins are critical to lubricity. A Gemini model of corneal epithelial cells (self-mated and matched) with intact membrane-bound mucins and glycocalyces (including MUC1, MUC4, and MUC16) was evaluated in the presence and absence of a purified gel-forming purified secretory mucin, MUC2. These experiments were performed under physiological contact pressures of ~ 600 Pa for 300 cycles of reciprocated sliding at 1 mm/s on a micro-biotribometer. With the addition of the MUC2 (5 wt.%), friction reductions from µ ~ 0.20 to µ ~ 0.08 were observed. In addition to the high friction seen in the glycocalyx, Gemini contacts with membrane-bound mucins and glycocalyces alone showed stick–slip events during sliding and large areas of cell damage after 300 cycles. Micro-rheology experiments using magnetic tweezers showed a yield stress for a MUC2 solution that is below the critical thresholds known to produce proinflammatory cytokines (< 40 Pa) and apoptosis (< 100 Pa). These secreted gel-forming mucins, such as MUC2, are, therefore, important for lubricity in Gemini epithelial interfaces.