Abstract

Physical topographical features and/or chemical stimuli to the extracellular matrix (ECM) provide essential cues that manipulate cell functions. From the physical point of view, contoured nanostructures are very important for cell behavior in general, and for cellular functions. From the chemical point of view, ECM proteins containing an RGD sequence are known to alter cell functions. In this study, the influence of integrated physical and chemical cues on a liver cell line (HepG2) was investigated. To mimic the physical cues provided by the ECM, amorphous TiO2 nanogratings with specific dimensional and geometrical characteristics (nanogratings 90 nm wide and 150 nm apart) were fabricated. To mimic the chemical cues provided by the ECM, the TiO2 inorganic film was modified by immobilization of the RGD motif. The hepatic cell line morphological and functional changes induced by simultaneously combining these diversified cues were investigated, including cellular alignment and the expression of different functional proteins. The combination of nanopatterns and surface modification with RGD induced cellular alignment and expression of functional proteins, indicating that physical and chemical cues are important factors for optimizing hepatocyte function.

Highlights

  • Understanding the relationship between human cells and their natural environment is very important for tissue engineering

  • We examined the integration of chemical and physical cues to study the influence of such integration on the enhancement of hepatic cellular behavior

  • Thereby, our findings suggest that surface nanofeatures with well-defined dimensions and chemical composition that imitate extracellular matrix (ECM) fibrillar structures and containing a specific motif (e.g., RGD) could be utilized to increase multiple cell functions, rather than using nanotopography or chemical cues alone

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Summary

Introduction

Understanding the relationship between human cells and their natural environment is very important for tissue engineering. A decrease in hepatocellular functionality generally occurs when liver cell lines are cultured on two-dimensional surfaces Living cells in their native environment are embedded in a complex of well-defined organic material and macromolecules called the extracellular matrix (ECM). Fibronectin, for example, is an ECM protein with a specific peptide sequence, Arginine-Glycine-Aspartic acid (RGD), that alters cellular attachment and spreading, as well as cell integration properties [12,13]. Both topographical features and chemical stimuli afforded by the ECM provide essential cues that fundamentally manipulate cell morphology [14], leading to alterations in migration [15], proliferation [16], and cytoskeleton organization [17]

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