A microdevice for studying intercellular electromechanical transduction in adult cardiac myocytes

Abstract

Intercellular electromechanical transduction in adult cardiac myocytes plays an important role in regulating heart function. The efficiency of intercellular electromechanical transduction has so far been investigated only to a limited extent, which is largely due to the lack of appropriate tools that can quantitatively assess the contractile performance of interconnected adult cardiac myocytes. In this paper we report a microengineered device that is capable of applying electrical stimulation to the selected adult cardiac myocyte in a longitudinally connected cell doublet and quantifying the intercellular electromechanical transduction by measuring the contractile performance of stimulated and un-stimulated cells in the same doublet. The capability of applying selective electrical stimulation on only one cell in the doublet is validated by examining cell contractile performance while blocking the intercellular communication. Quantitative assessment of cell contractile performance in isolated adult cardiac myocytes is performed by measuring the cell length change. The proof-of-concept assessment of gap junction performance shows that the device is useful in studying the efficiency of gap junctions in adult cardiac myocytes that are most relevant to synchronized pumping performance of native myocardium. Collectively, this work provides a quantitative tool for studying intercellular electromechanical transduction and is expected to develop a comprehensive understanding of the role of intercellular communications in various heart diseases.

Electrical and mechanical stimulation of cardiac cells and tissue constructs

“…One way to translate in vitro results to clinical applications is through the development of culture platforms that mimic native function in a high-throughput, miniaturized platform using tools such as microfluidic channels, micro-devices, and chips for testing the safety and efficacy of drugs via CM response [327–333]. Microscale platforms are beneficial due to the small size, which enables high throughput analyses, utilization of limited cell numbers, and adequate oxygen and nutrient delivery, enabling analysis of cellular response to various drug formulations as well as concentrations without draining resources.…”

UV-nanoimprint lithography as a tool to develop flexible microfluidic devices for electrochemical detection

“…23,24 Comparatively, inkjet-printing can be used for high throughput, low-cost and continuous fabrication processes without the need for metal removal. This method also offers the advantage of small feature sizes, rapid prototyping and targeted patterning.…”

Engineering Cardiac Cell JunctionsIn Vitroto Study the Intercalated Disc

“…In addition to the studies described above, micropatterned cardiac cell pairs have been used as a model system for understanding gap junction traffi cking (Zhang et al, 2014) and coupling between cardiac myocytes and other cell types, such as mesenchymal stem cells (Pedrotty et al, 2008). New microdevices have been developed to selectively apply electrical stimulation to only one myocyte in a pair, a tool useful for studying the effi ciency of gap junction coupling (Zhang et al, 2013). Instead of culturing pairs of cardiac myocytes on extracellular matrix proteins, another approach has been to culture isolated myocytes directly on substrates coated with cadherin such that myocytes form pseudo-cell -cell junctions directly with the substrate (Ganz et al, 2006;Chopra et al, 2011).…”