Engineered tissue hybrids for bioelectronic recording and control
21st September 2023
Timing : 1 pm EST
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For a list of all talks at the NanoBio seminar Series Fall'23, see here
We recently developed a multi-electrode array (MEA) platform that could integrate with cardiac monolayers at up to 32 spatially-distinct locations in vitro. In the first part of this talk we will discuss our recent heart-on-a-chip platform which integrated both extra- and intracellular recording elements for monitoring cardiac electrophysiology during episodes of acute hypoxia. This system allowed us to monitor not only cell-cell communication (e.g., wavefront propagation) but also action potentials (APs) at several spatially-distinct regions simultaneously. Our platform provided a unique route toward understanding the role of hypoxia on ion channel dynamics. For example, we found that APs narrowed during hypoxia, consistent with proposed mechanisms by which oxygen deficits activate ATP-dependent K+ channels that promote membrane repolarization.
In the second part of this talk we discuss an integrated optogenetic and bioelectronic platform for stable and long-term modulation and monitoring of cardiomyocyte function. Optogenetic inputs were achieved through expression of a photoactivatable adenylyl cyclase (bPAC), that when exposed to blue light caused a dose-dependent and time-limited increase in intracellular cyclic AMP concentration and, subsequently, autonomous cardiomyocyte beat rate. Bioelectronic outputs from the MEA provided real-time readouts of cardiomyocyte behavior in response to optical modulation. Irradiation at 24 μW/mm2 resulted in a ca. 17% increase in beat rate within 20-25 minutes of irradiation. Multiplexed readouts revealed that wavefront propagation rates throughout the monolayer remained constant between “on” and “off” states, demonstrating that optical modulation did not affect intercellular coupling. In addition, bPAC activation could be cycled through repeated “on” and “off” states via time-limited illumination or in a gradient fashion with 0.03-24 μW/mm2 illumination. Cardiomyocytes could be modulated reproducibly over at least four days, demonstrating that bPAC expression as well as the bioelectronic interface were stable throughout that period.
Taken together, our studies demonstrate the feasibility of bioelectronic and optical techniques for monitoring and modulating function in the heart or other tissues. We will discuss recent efforts in our lab toward 3D bioelectronics-embedded tissues and closed-loop feedback systems. We will also discuss potential clinical applications for disorders in the heart or brain.
Dr. Brian Timko
Assistant Professor
Department of Biomedical Engineering
Tufts University
Brian Timko is an assistant professor in the Department of Biomedical Engineering at Tufts University. He earned his PhD at Harvard University under the mentorship of Charles Lieber. During that time he studied silicon nanowires and demonstrated the first subcellular, nanoelectronic interfaces with living systems, including cultured neurons and cardiomyocytes as well as heart and brain tissues. The then completed postdoctoral studies as an NIH NRSA fellow at MIT in the laboratories of Robert Langer and Daniel Kohane. There he studied fundamental interactions between nanowires and 3D engineered cardiac tissues and demonstrated that nanowires could recapitulate the nanotopography of the extracellular matrix, guiding cardiomyocyte assembly and tissue maturation. From there he was an Instructor at Boston Children’s Hospital and Harvard Medical School where he studied plasmonic gold nanomaterials and their utility in near infrared-triggered drug delivery systems. Brian’s laboratory at Tufts focuses on bioelectronics and is developing novel materials to achieve two-way electronic communication as well as bioelectronic scaffolds to achieve seamless device integration with engineered tissues. Brian received the inagural Nano Research Young Innovators Award in Nanobiotechnology, and currently serves as an Associate Editor for the journal Bioelectronic Medicine. His lab is receiving funding from an NSF CAREER Award and American Heart Association Transformational Project Award.
Assistant Professor
Department of Biomedical Engineering
Tufts University
Brian Timko is an assistant professor in the Department of Biomedical Engineering at Tufts University. He earned his PhD at Harvard University under the mentorship of Charles Lieber. During that time he studied silicon nanowires and demonstrated the first subcellular, nanoelectronic interfaces with living systems, including cultured neurons and cardiomyocytes as well as heart and brain tissues. The then completed postdoctoral studies as an NIH NRSA fellow at MIT in the laboratories of Robert Langer and Daniel Kohane. There he studied fundamental interactions between nanowires and 3D engineered cardiac tissues and demonstrated that nanowires could recapitulate the nanotopography of the extracellular matrix, guiding cardiomyocyte assembly and tissue maturation. From there he was an Instructor at Boston Children’s Hospital and Harvard Medical School where he studied plasmonic gold nanomaterials and their utility in near infrared-triggered drug delivery systems. Brian’s laboratory at Tufts focuses on bioelectronics and is developing novel materials to achieve two-way electronic communication as well as bioelectronic scaffolds to achieve seamless device integration with engineered tissues. Brian received the inagural Nano Research Young Innovators Award in Nanobiotechnology, and currently serves as an Associate Editor for the journal Bioelectronic Medicine. His lab is receiving funding from an NSF CAREER Award and American Heart Association Transformational Project Award.