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Open AccessArticle

The Effect of Matrix Stiffness on Human Hepatocyte Migration and Function—An In Vitro Research

Key Laboratory of Biorheological Science and Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China
Authors to whom correspondence should be addressed.
Polymers 2020, 12(9), 1903;
Received: 25 June 2020 / Revised: 8 August 2020 / Accepted: 18 August 2020 / Published: 24 August 2020
(This article belongs to the Section Polymer Applications)
The extracellular matrix (ECM) regulates cellular function through the dynamic biomechanical and biochemical interplay between the resident cells and their microenvironment. Pathologically stiff ECM promotes phenotype changes in hepatocytes during liver fibrosis. To investigate the effect of ECM stiffness on hepatocyte migration and function, we designed an easy fabricated polyvinyl alcohol (PVA) hydrogel in which stiffness can be controlled by changing the concentration of glutaraldehyde. Three stiffnesses of hydrogels corresponding to the health of liver tissue, early stage, and end stage of fibrosis were selected. These were 4.8 kPa (soft), 21 kPa (moderate), and 45 kPa (stiff). For hepatocytes attachment, the hydrogel was coated with fibronectin. To evaluate the optimal concentration of fibronectin, hydrogel was coated with 0.1 mg/mL, 0.01 mg/mL, 0.005 mg/mL, or 0.003 mg/mL fibronectin, and the migratory behavior of single hepatocyte cultured on different concentrations of fibronectin was analyzed. To further explore the effect of substrate stiffness on hepatocyte migration, we used a stiffness controllable commercial 3D collagen gel, which has similar substrate stiffness to that of PVA hydrogel. Our result confirmed the PVA hydrogel biocompatibility with high hepatocytes survival. Fibronectin (0.01 mg/mL) promoted optimal migratory behavior for single hepatocytes. However, for confluent hepatocytes, a stiff substrate promoted hepatocellular migration compared with the soft and moderate groups via enhancing the formation of actin- and tubulin-rich structures. The gene expression analysis and protein expression analysis showed that the stiff substrate altered the phenotype of hepatocytes and induced apoptosis. Hepatocytes in stiff 3D hydrogel showed a higher proportion of cell death and expression of filopodia. View Full-Text
Keywords: substrate stiffness; hepatocyte; migration; hepatocyte migration; hepatocyte function substrate stiffness; hepatocyte; migration; hepatocyte migration; hepatocyte function
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Xia, T.; Zhao, R.; Feng, F.; Yang, L. The Effect of Matrix Stiffness on Human Hepatocyte Migration and Function—An In Vitro Research. Polymers 2020, 12, 1903.

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