CellStretch · A Cardiomyocyte Workout: Using Dielectric Elastomer Actuators for Mechanical Stimulation of in-vitro Cells

A Cardiomyocyte Workout:Using Dielectric Elastomer Actuators for Mechanical Stimulation of in-vitro Cells

Most of what is known in the realm of cell biology is the result of painstaking experiments of in vitro cell cultures. Removing tissue from a living organism and placing it into the controlled environment of a petri dish allows for complete control of the experiment. No longer obscured by the complexity of an entire living body, in vitro cell cultures enabled physiologists to use microscopy, biochemistry, and electrophysiology to reveal the basic biological functions of both tissues and single cells. This led to great advances in our understanding of cell metabolism, toxicology, drug screening, fertility, and genetics. Although temperature, chemical composition, and electrical signaling can be precisely controlled, glassware is not only hard but also static. There is no bending or stretching, no movement. And what is life without motion? Cells ‘feel’ their surroundings, push back against external perturbations and self-organize to assert themselves in a dynamic world. But a Petri dish is dead: a hard, unyielding boundary condition, a sterile well where cells are cultured and experimented on from hours to days, until they die. We developed in this project a mechanically active device for new kinds of in vitro cell physiology experiments. Through the use of Dielectric Elastomer Actuators (DEA), a stretchable membrane replaces the petri dish. Cells can be grown on such ‘artificial muscles’ and exposed to well defined strains and strain rates; this represents a much closer approximation to their native environment. DEAs expand the experimental parameter space of in vitro studies to include the all-important mechanical degree of freedom; this addresses the mechanosensitive response of living cells. In this context, we were able to develop not only a mechanically dynamic cell culture well, but also an integrated a micro electrode array (MEA) enabling electrical sensing and stimulation in addition to the mechanical dynamics. This allowed us to monitor the electromechancial feedback of a strand of cardiomyocytes by tracking the impulse propagation. We were able to determine not only the sensitivity to strain amplitude but also the response to changing strain rates. The underlying mechanisms of arrhythmias causing cardiac failure, currently the number one cause of death in the EU, can now be studied with the inclusion of mechano-electrical feedback (MEF). Adverse mechano-electrical feedback in the heart is dramatically illustrated by accidents where people die after the thorax is struck powerfully, e.g. by a football. Much subtler, but quantitatively much more relevant, ad-verse mechano-electrical feedback is thought to occur in diseased hearts in patients with high blood pressure, valvular heart diseases, and infarction. The CellStretch project developed a fundamentally new device that can both generate the strain rates associated with traumatic interactions and simultaneously track the electrophysiology of the cell strand.

Data: CORDIS, © European Union