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Modulation of hepatocyte phenotype in vitro via chemomechanical tuning of polyelectrolyte multilayers

Paper ID Volume ID Publish Year Pages File Format Full-Text
9260 623 2009 8 PDF Available
Title
Modulation of hepatocyte phenotype in vitro via chemomechanical tuning of polyelectrolyte multilayers
Abstract

It is increasingly appreciated that since cell and tissue functions are regulated by chemomechanical stimuli, precise control over such stimuli will improve the functionality of tissue models. However, due to the inherent difficulty in decoupling these cues as presented by extracellular materials, few studies have explored the independent modulation of biochemical and mechanical stimuli towards the manipulation of sustained cellular processes. Here, we demonstrate that both mechanical compliance and ligand presentation of synthetic, weak polyelectrolyte multilayers (PEMs) can be tuned independently to influence the adhesion and liver-specific functions of primary rat hepatocytes over extended in vitro culture (two weeks). These synthetic PEMs exhibited elastic moduli E ranging over 200 kPa < E < 142 MPa, as much as one thousand-fold more compliant than tissue-culture polystyrene (E ∼ 2.5 GPa). The most compliant of these PEM substrata promoted hepatocyte adhesion and spheroidal morphology. Subsequent modification of PEMs with type I collagen and the proteoglycan decorin did not alter substrata compliance, but enhanced the retention of spheroids on surfaces and stabilized hepatic functions (albumin and urea secretion, CYP450 detoxification activity). Decorin exhibited unique compliance-mediated effects on hepatic functions, down-regulating the hepatocyte phenotype when presented on highly compliant substrata while up-regulating hepatocyte functions when presented on increasingly stiffer substrata. These results show that phenotypic functions of liver models can be modulated by leveraging synthetic polymers to study and optimize the interplay of biochemical and mechanical cues at the cell–material interface. More broadly, these results suggest an enabling approach for the systematic design of functional tissue models applied to drug screening, cell-based therapies and fundamental studies in development, physiology and disease.

Keywords
Hepatocyte; Polyelectrolyte multilayers; Compliance; Surface modification; Chemomechanics
First Page Preview
Modulation of hepatocyte phenotype in vitro via chemomechanical tuning of polyelectrolyte multilayers
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 6, February 2009, Pages 1113–1120
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering