High-speed mechano-active multielectrode array for investigating rapid stretch effects on cardiac tissue

Matthias Imboden,Alexandre Poulin,Herbert Shea,Samuel Rosset,Christian Dellenbach,Etienne De Coulon,Stephan Rohr

doi:10.1038/s41467-019-08757-2

Matthias Imboden, Alexandre Poulin + Show 5 more

Open Access

https://doi.org/10.1038/s41467-019-08757-2

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Abstract

Systematic investigations of the effects of mechano-electric coupling (MEC) on cellular cardiac electrophysiology lack experimental systems suitable to subject tissues to in-vivo like strain patterns while simultaneously reporting changes in electrical activation. Here, we describe a self-contained motor-less device (mechano-active multielectrode-array, MaMEA) that permits the assessment of impulse conduction along bioengineered strands of cardiac tissue in response to dynamic strain cycles. The device is based on polydimethylsiloxane (PDMS) cell culture substrates patterned with dielectric actuators (DEAs) and compliant gold ion-implanted extracellular electrodes. The DEAs induce uniaxial stretch and compression in defined regions of the PDMS substrate at selectable amplitudes and with rates up to 18 s−1. Conduction along cardiomyocyte strands was found to depend linearly on static strain according to cable theory while, unexpectedly, being completely independent on strain rates. Parallel operation of multiple MaMEAs provides for systematic high-throughput investigations of MEC during spatially patterned mechanical perturbations mimicking in-vivo conditions.

Highlights

Systematic investigations of the effects of mechano-electric coupling (MEC) on cellular cardiac electrophysiology lack experimental systems suitable to subject tissues to in-vivo like strain patterns while simultaneously reporting changes in electrical activation
To achieve faster strain rates, we developed an experimental system (i) that is based on self-contained, mechanically active cell culture wells, (ii) that permits the reproducible application of defined levels of strain at predefined strain rates to cultured excitable cells, and (iii) that allows for continuous determinations of conduction velocities immediately after strain application
An overview of the components of the mechano-active multielectrode array (MaMEA) system is presented in Fig. 1 and the operating principle of the dielectric actuator (DEA) is outlined in Supplementary Fig. 1 The modular device is built around a cell culture well whose bottom consists of a pre-stretched polydimethylsiloxane (PDMS) membrane that is sandwiched between two ring-shaped printed circuit boards (PCBs) (Fig. 1a, e)

Summary

Introduction

Systematic investigations of the effects of mechano-electric coupling (MEC) on cellular cardiac electrophysiology lack experimental systems suitable to subject tissues to in-vivo like strain patterns while simultaneously reporting changes in electrical activation. We describe a self-contained motor-less device (mechano-active multielectrode-array, MaMEA) that permits the assessment of impulse conduction along bioengineered strands of cardiac tissue in response to dynamic strain cycles. Experimental investigations of the mechanisms underlying these phenomena require cardiac tissue to be subjected to strain amplitudes and strain rates that range from those encountered during the normal pump cycle of the heart to those present under pathophysiological conditions while permitting the simultaneous monitoring of electrophysiological parameters of interest. Experiments with bioengineered strands of rat ventricular cardiomyocytes revealed that, surprisingly, conduction velocity is independent on strain rates even if rates surpass physiological levels by an order of magnitude

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