Mechanical Regulation of Oral Epithelial Barrier Function

Published

April 25, 2023

Author(s)

Eun Jin Lee, Yoontae Kim, Paul Salipante, Anthony Kotula, Dana Graves, Stella Alimperti

Abstract

Epithelial cell function is modulated by mechanical forces imparted by the extracellular environment. The transmission of forces onto the cytoskeleton by modalities such as mechanical stress and matrix stiffness is necessary to address by the development of new experimental models that permit finely tuned cell mechanical challenges. Herein, we developed an epithelial tissue culture model, named the 3D Oral Epi-mucosa platform, to investigate the role mechanical cues in the epithelial barrier. In this platform, low-level mechanical stress (0.1 kPa) is applied to oral keratinocytes, which lie on 3D fibrous collagen (Col) gels whose stiffness is modulated by different concentrations or the addition of other factors such as fibronectin (FN). Our results show that cells lying on intermediate Col (3 mg/mL; stiffness = 30 Pa) demonstrated lower epithelial leakiness compared with soft Col (1.5 mg/mL; stiffness = 10 Pa) and stiff Col (6 mg/mL; stiffness = 120 Pa) gels, indicating that stiffness modulates barrier function. In addition, the presence of FN reversed the barrier integrity by inhibiting the interepithelial interaction via E-cadherin and Zonula occludens-1. Overall, the 3D Oral Epi-mucosa platform, as a new in vitro system, will be utilized to identify new mechanisms and develop future targets involved in mucosal disease.

Citation

Bioengineering

Pub Type

Journals

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Keywords

epithelium, oral mucosa, microfluidics, mechanical stress, pressure, keratinocytes, organ-on-a-chip, fibronectin, barrier function.

Citation

Lee, E. , Kim, Y. , Salipante, P. , Kotula, A. , Graves, D. and Alimperti, S. (2023), Mechanical Regulation of Oral Epithelial Barrier Function, Bioengineering, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=936200 (Accessed April 19, 2024)