Electrical Stimulation of Biological Matter

Abstract

Electric signaling is found throughout biological systems to facilitate coordination of collective activities. Although often associated with the brain and nervous system, many other cell types communicate electrically. In this thesis the activity patterns of cardiomyocytes were studied. To obtain a supply of cardiomyocytes, human induced pluripotent stem cells (hiPSCs) were differentiated into cardiomyocytes through the addition of two separate small molecules: CHIR99021 and IWP2. Beating patterns were analyzed in the absence and presence of external electrical stimulation using particle image velocimetry. To increase the ease and capability of these experiments, a custom stimulation device and firmware to control this device were developed. The design process is thoroughly described in this report. Cardiomyocytes were found to be highly responsive to electrical stimulation although the nature of this response varied. A number of metrics were explored to best characterize these responses. In most cases, the speed of the movements of the cells increased, although this increase did not always have specificity to the axis along which electrical stimulation was applied. Changes in the frequency spectra of cardiomyocyte motion in response to electric stimulation were found. Simulations were developed to better understand the underlying dynamics by which signals propagate through cardiac tissue and study the impact of non-electrically conductive cells interspersed in a network of cardiomyocytes. Because the parameter space of potential stimulation patterns is incredibly vast and the number of actual cardiomyocyte tissues available is finite, the simulation software enables the consideration of scientific questions that would not otherwise be feasible. The combination of the hiPSC derived cardiomyocytes, the stimulation device, the analysis software, and the simulation pipeline developed in this thesis can serve as a full stack to investigate signal propagation through cardiac tissue with potential applications in uncovering new mechanisms behind cardiac diseases and creating novel therapies. This work on cardiomyocytes is part of a broader effort to communicate with electrically excitable biological systems. This thesis builds on previous research that I have pursued focused on delivering spatially localized stimulation to mammalian kidney tissues and decoding the electrical activity of neural organoids.