Plasma polymerized bio-interface directs fibronectin adsorption and functionalization to enhance "epithelial barrier structure" formation via FN-ITG β1-FAK-mTOR signaling cascade

等离子体聚合生物界面指导纤连蛋白吸附和功能化,通过 FN-ITG β1-FAK-mTOR 信号级联增强“上皮屏障结构”形成

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作者:Shoucheng Chen #, Zhuwei Huang #, Rahul Madathiparambil Visalakshan, Haiwen Liu, Akash Bachhuka, You Wu, Panthihage Ruvini L Dabare, Pu Luo, Runheng Liu, Zhuohong Gong, Yin Xiao, Krasimir Vasilev, Zhuofan Chen, Zetao Chen

Background

Transepithelial medical devices are increasing utilized in clinical practices. However, the damage of continuous natural epithelial barrier has become a major risk factor for the failure of epithelium-penetrating implants. How to increase the "epithelial barrier structures" (focal adhesions, hemidesmosomes, etc.) becomes one key research

Conclusion

This study offers an effective perspective to overcome the current dilemma of the inferior interface-epithelial integration by in situ protein absorption and functionalization, which may advance the development of functional transepithelial biointerfaces. Tuning the surface chemistry by plasma polymerization can control the adsorption of fibronectin and functionalize it by exposing functional protein domains. The functionalized fibronectin can bind to human gingival epithelial cell membrane integrins to activate epithelial barrier structure related signaling pathway, which eventually enhances the formation of epithelial barrier structure.

Methods

Herein, we fabricated three plasma polymerized bio-interfaces possessing controllable surface chemistry. Their capacity to adsorb and functionalize fibronectin (FN) from serum protein was compared by Liquid Chromatography-Tandem Mass Spectrometry. The underlying mechanisms were revealed by molecular dynamics simulation. The response of gingival epithelial cells regarding the formation of epithelial barrier structures was tested.

Results

Plasma polymerized surfaces successfully directed distinguished protein adsorption profiles from serum protein pool, in which plasma polymerized allylamine (ppAA) surface favored adsorbing adhesion related proteins and could promote FN absorption and functionalization via electrostatic interactions and hydrogen bonds, thus subsequently activating the ITG β1-FAK-mTOR signaling and promoting gingival epithelial cells adhesion.

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