Effect of laminin, polylysine and cell medium components on the attachment of human hepatocellular carcinoma cells to cellulose nanofibrils analyzed by surface plasmon resonance

Xue Zhang,Tapani Viitala,Riina Harjumäki,Alma Kartal-Hodzic,Juan José Valle-Delgado,Monika Österberg

doi:10.1016/j.jcis.2020.09.080

Xue Zhang, Tapani Viitala + Show 4 more

Open Access

https://doi.org/10.1016/j.jcis.2020.09.080

Copy DOI

Abstract

The development of in vitro cell models that mimic cell behavior in organs and tissues is an approach that may have remarkable impact on drug testing and tissue engineering applications in the future. Plant-based, chemically unmodified cellulose nanofibrils (CNF) hydrogel is a natural, abundant, and biocompatible material that has attracted great attention for biomedical applications, in particular for three-dimensional cell cultures. However, the mechanisms of cell-CNF interactions and factors that affect these interactions are not yet fully understood. In this work, multi-parametric surface plasmon resonance (SPR) was used to study how the adsorption of human hepatocellular carcinoma (HepG2) cells on CNF films is affected by the different proteins and components of the cell medium. Both human recombinant laminin-521 (LN-521, a natural protein of the extracellular matrix) and poly-l-lysine (PLL) adsorbed on CNF films and enhanced the attachment of HepG2 cells. Cell medium components (glucose and amino acids) and serum proteins (fetal bovine serum, FBS) also adsorbed on both bare CNF and on protein-coated CNF substrates. However, the adsorption of FBS hindered the attachment of HepG2 cells to LN-521- and PLL-coated CNF substrates, suggesting that serum proteins blocked the formation of laminin-integrin bonds and decreased favorable PLL-cell electrostatic interactions. This work sheds light on the effect of different factors on cell attachment to CNF, paving the way for the utilization and optimization of CNF-based materials for different tissue engineering applications.

Highlights

There is an increasing demand for accurate organ models for toxicology testing of drugs and chemicals and for organ replacements
The chemically unmodified, wood-derived cellulose nanofibril hydrogel (CNF) is a natural, abundant, and biocompatible material that has emerged in the last years as a promising matrix for threedimensional (3D) cell cultures [6,7]
The use of CNF to its full potential in tissue engineering and other biomedical applications requires a deep understanding of the cell-CNF interactions, as well as how different factors, like proteins and cell medium components, may affect those interactions

Summary

Introduction

There is an increasing demand for accurate organ models for toxicology testing of drugs and chemicals and for organ replacements. The development of in vitro cell models that mimic the response of cells in vivo has attracted increasing attention lately [1]. Since the liver is the main organ responsible for drug metabolism and xenobiotic biotransformation, hepatic cell lines have been used in biomedical research for decades. The human hepatocellular carcinoma cell line HepG2 has been a popular model for liver disease investigations, drug tests and genotoxicity studies [2]. HepG2 cells retain most of the main properties of normal liver parenchymal cells like, for instance, the biosynthesis of plasma proteins and the expression of many enzymes for xenobiotic biotransformation [3,4]

Methods

Results

Conclusion