Cell adhesion promotion strategies for signal transduction enhancement in microelectrode array in vitro electrophysiology: An introductory overview and critical discussion

Microelectrode arrays (MEAs) find application both in vitro and in vivo to record and stimulate electrical activity in electrogenic cells such as neurons, cardiomyocytes, pancreatic beta cells or immortalized cell lines derived therefrom (e.g., PC12, HL-1). In MEA electrophysiology, the quality of the predominantly extracellularly recorded or elicited electrical signals strongly depends on the distance, strength and stability of the interfacial contact between the electrogenic cells and an electrode. Decorating the substrate or electrode with biochemical adhesion factors and physical guidance cues does not only determine the tightness of that junction, but it also modulates substrate biocompatibility, its biostability, cell differentiation as well as cell fate. If an interface is furthermore topologically, chemically or physically patterned or constrained, neural interconnectivity may be steered towards directional organization. In this introductory and selective overview, we briefly discuss adhesion events at the chemical and biological level, review the general role and mechanisms of cell adhesion in (neuro)biology, then explore how cells adhere to artificial substrates. This will lead to the discussion of popular strategies for enhancing and steering interfacial interactions at the bio-hardware boundary with particular focus on MEA substrates. It will include a critical treatment of open issues with respect to the origin and shape of extracellularly recorded signals and their modulation by cell-culture-inherent events.