Mechanical Regulation of Oral Epithelial Barrier Function

被引:15
|
作者
Lee, Eun-Jin [1 ,2 ,3 ]
Kim, Yoontae [1 ]
Salipante, Paul [4 ]
Kotula, Anthony P. [4 ]
Lipshutz, Sophie [1 ]
Graves, Dana T. [5 ]
Alimperti, Stella [1 ]
机构
[1] Georgetown Univ, Sch Med, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA
[2] Natl Inst Stand & Technol, Microsyst & Nanotechnol Div, Phys Measurement Lab, Gaithersburg, MD 20899 USA
[3] Univ Maryland, Coll Comp Math & Nat Sci, Dept Chem & Biochem, College Pk, MD 20742 USA
[4] Natl Inst Stand & Technol, Mat Sci & Engn Div, Mat Measurement Lab, Gaithersburg, MD 20899 USA
[5] Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA 19104 USA
来源
BIOENGINEERING-BASEL | 2023年 / 10卷 / 05期
基金
美国国家卫生研究院;
关键词
epithelium; oral mucosa; microfluidics; mechanical stress; pressure; keratinocytes; organ-on-a-chip; fibronectin; barrier function;
D O I
10.3390/bioengineering10050517
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 diseases.
引用
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页数:16
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