Abstract

Coupling of cells to biomaterials is a prerequisite for most biomedical applications; e.g., neuroelectrodes can only stimulate brain tissue in vivo if the electric signal is transferred to neurons attached to the electrodes’ surface. Besides, cell survival in vitro also depends on the interaction of cells with the underlying substrate materials; in vitro assays such as multielectrode arrays determine cellular behavior by electrical coupling to the adherent cells. In our study, we investigated the interaction of neurons and glial cells with different electrode materials such as TiN and nanocolumnar TiN surfaces in contrast to gold and ITO substrates. Employing single-cell force spectroscopy, we quantified short-term interaction forces between neuron-like cells (SH-SY5Y cells) and glial cells (U-87 MG cells) for the different materials and contact times. Additionally, results were compared to the spreading dynamics of cells for different culture times as a function of the underlying substrate. The adhesion behavior of glial cells was almost independent of the biomaterial and the maximum growth areas were already seen after one day; however, adhesion dynamics of neurons relied on culture material and time. Neurons spread much better on TiN and nanocolumnar TiN and also formed more neurites after three days in culture. Our designed nanocolumnar TiN offers the possibility for building miniaturized microelectrode arrays for impedance spectroscopy without losing detection sensitivity due to a lowered self-impedance of the electrode. Hence, our results show that this biomaterial promotes adhesion and spreading of neurons and glial cells, which are important for many biomedical applications in vitro and in vivo.

Highlights

  • Many cellular processes such as proliferation and migration rely on the ability of cells to adhere to a surrounding medium such as the extracellular matrix (ECM) or a biomaterial [1]

  • By further increasing the surface area of titanium nitride (TiN) with a nanocolumnar pattern, we have previously shown that neurons and glial cells cultured on these surfaces exhibit a much better proliferation behavior, in contrast to conventional electrode materials such as gold and indium-tin-oxide (ITO) [30]

  • Thereby increase cell size, is usually coupled to an increased number of adhesion points, which in turn leads cell size, is usually coupled to an increased number ofofadhesion points, which in turn of cell size, iscell usually coupled to an increased number of points, which in leads turn to enhanced adhesion and improved bioactivity theadhesion underlying substrate material to enhanced cell adhesion and improved bioactivity of the underlying substrate material leads to enhanced cell adhesion and improved bioactivity of the underlying substrate

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Summary

Introduction

Many cellular processes such as proliferation and migration rely on the ability of cells to adhere to a surrounding medium such as the extracellular matrix (ECM) or a biomaterial [1]. Cells express specific proteins, such as fibronectin or laminin, which can be deposited onto the biomaterial. This enables the cells to form specific adhesion points via surface receptors connecting to the previously deposited proteins. First adhesion sites for cells in contact with biomaterials can occur within seconds when early focal complexes form [2]. Maturation of this soft binding step to focal adhesion results in specific adhesion sites in which cellular adhesion receptors interact with ECM molecules and form mature adhesion complexes [2,3]

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