Friction-Induced Inflammation: Cells, Gels, and Shear

Angela A. Pitenis1, Juan Manuel Urueña1, Samuel M. Hart1, Padraic P. Levings2, W. Gregory Sawyer1,3,4


1Department of Mechanical and Aerospace Engineering

2Department of Orthopaedics and Rehabilitation

3J. Crayton Pruitt Family Department of Biomedical Engineering

4Department of Materials Science and Engineering

University of Florida, Gainesville, Florida 32611, USA

Abstract:  Friction-induced inflammation is a hypothesis that implicates interfacial shear stress as a trigger for the production of pro-inflammatory cytokines, which in severe cases may lead to pain and chronic inflammation. Ocular lubricity is dependent on tear film stability and the health of the corneal and conjunctival epithelium, though the insertion of a soft contact lens disrupts the ocular system and may subject the epithelia to increased shear stresses. The effects of frictional shear stresses on cellular responses were experimentally measured in vitro by sliding soft hydrogel probes against human corneal epithelial (hTCEpi) cell monolayers for 900 reciprocating cycles (5.5 h) using two normal forces: 500 µN and 1,000 µN, giving t ~30 Pa and t ~60 Pa shear stresses, respectively. Compared to a control population, molecular biology assays revealed frictional shear stresses of t ~60 Pa increased gene expression of pro-inflammatory cytokine gene Interleukin-6 (IL-6) by ~800%, and pro-apoptotic gene DNA Damage Inducible Transcript 3 (DDIT3) by nearly 1,000%. These results suggest that frictional shear stress may be responsible for inducing inflammatory responses in corneal epithelial cells in vitro.