INSPIRE: Optogenetic Control of the Human Heart - Turning Light into Force

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This INSPIRE Research Award is co-funded by the Biomechanics and Mechanobiology (BMMB) and the Mechanics of Materials (MoM) Programs in the Division of Civil, Mechanical, and Manufacturing Innovation (CMMI), and the Biophotonics Program in the Division of Chemical, Biological, Environmental, and Transport Systems (CBET), both in the Directorate for Engineering (ENG). In the United States alone, almost half a million people die each year as a result of heart rhythm disorders. Despite its invasive nature, electrical stimulation remains the gold standard treatment for rhythm disturbances in the heart. This project challenges the conventional wisdom of how to manipulate electrical signals in the human heart. The long-term goal is to establish a novel technology to control heart rhythm disorders, safely, precisely, and remotely, simply by means of light using a new concept known as optogenetics. The objective of this research is to create a biological pacemaker of genetically engineered cells that will allow us to decipher the basic mechanisms by which optogenetics can regulate the pump function of the heart. The research approach is a systematic theoretical, experimental, and computational characterization of photostimulation across four biological scales.This work is highly innovative, since it adopts optogenetics, for the first time, to control human heart cells and tissue. It combines concepts, methods, and recent developments in optics, genetics, stem cell biology, electrophysiology, mechanobiology, biomechanics, mathematical modeling, and computer simulation. Its unusual interdisciplinary nature has the potential to reveal fundamental mechanisms of the photoelectrochemistry and mechanics of living systems. This knowledge gain will stimulate discovery in optogenetics and initiate new technologies to manipulate excitable cells. The transformative potential of the work is that it may open new avenues to support the design of novel therapies for various types of neuronal, musculoskeletal, pancreatic, and cardiac disorders such as depression, schizophrenia, paralysis, diabetes, pain syndromes, and cardiac arrhythmias.