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A Biomimetic Model for Liver Cancer to Study Tumor-Stroma Interactions in a 3D Environment with Tunable Bio-Physical Properties
Published on: August 7, 2020
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Polyisocyanide hydrogels with tunable nonlinear elasticity mediate liver carcinoma cell functional response
Zixin Liu1, Jingxuan Fu2, Hongbo Yuan3
1Key Laboratory of Hebei Province for Molecular Biophysics, Institute of Biophysics, School of Science, Hebei University of Technology, Tianjin 300401, PR China.
Acta Biomaterialia
|June 19, 2022
Summary
Nonlinear tissue mechanics, specifically strain-stiffening, impact liver cancer cell behavior. Biomimetic hydrogels show that increased stiffness promotes HepG2 cell motility and invasiveness, affecting key cancer biomarkers.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Materials Science
Background:
- Hepatocellular carcinoma (HCC) progression is linked to altered liver tissue mechanics, including fibrosis.
- While linear elasticity is studied, the liver's nonlinear strain-stiffening behavior is crucial for cell-microenvironment interactions.
- Understanding these nonlinear properties is vital for developing effective cancer therapies.
Purpose of the Study:
- To investigate the influence of tunable nonlinear mechanical properties, specifically strain-stiffening, on HepG2 liver cancer cell behavior.
- To utilize biomimetic polyisocyanides (PIC) hydrogels with varying critical stress to mimic liver tissue mechanics.
- To explore the relationship between material properties and cellular responses like motility, invasiveness, and biomarker expression.
Main Methods:
- Fabrication of polyisocyanides (PIC) hydrogels with tunable nonlinear mechanical properties by altering polymer length.
- Grafting of GRGDS peptide onto hydrogels to enhance cell adhesion.
- Culturing HepG2 liver cancer cells on PIC hydrogels with different critical stress values.
- Assessing cell motility, invasiveness, actin stress fiber formation, YAP expression and translocation, and KCa3.1 channel expression.
Main Results:
- PIC hydrogels with higher critical stress (longer polymer chains) significantly promoted HepG2 cell motility and invasiveness compared to those with lower critical stress.
- Increased actin stress fiber formation and higher expression and nuclear translocation of YAP were observed in cells on stiffer PIC gels.
- The expression of KCa3.1 potassium channel, a biomarker for HCC, was upregulated on stiffer PIC gels and could be suppressed by inhibiting actin fiber formation.
Conclusions:
- The strain-stiffening property of biomimetic PIC hydrogels significantly influences liver cancer cell behavior, including motility and invasiveness.
- PIC hydrogel mechanics modulate cytoskeletal organization (actin stress fibers) and mechanotransduction pathways (YAP).
- PIC hydrogel stiffness affects KCa3.1 potassium channel expression via cytoskeletal regulation, highlighting a novel mechanism in HCC progression and potential therapeutic targeting.
