About the Lab

The Disease Biophysics Group (DBG) at Harvard University is an interdisciplinary team of biologists, physicists, engineers and material scientists actively researching the structure/function relationship in cardiac, neural, and vascular smooth muscle tissue engineering. We seek to quantify cellular mechanotransduction at the single-cell and tissue level to understand the effect on electrophysiology and disease states.

 Microphysiological systems (MPS).

Since 2004, the Disease Biophysics Group (DBG) has led the study of heart , and other organ systems, through the development of microphysiological systems (MPS). These "heart-on-a-chip" platforms integrate human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into microengineered environments that mimic the native mechanical and electrical properties of cardiac tissue. A landmark 2014 study used this technology to model Barth syndrome, a rare genetic heart disorder, providing the first tissue-based evidence of how mitochondrial dysfunction impairs contractile force. More recent advances include the development of non-genetic optical stimulation methods, such as organic phototransducers, which allow researchers to pace engineered heart tissues and study calcium propagation without invasive electrodes, significantly extending the longevity and utility of these models for long-term drug toxicity screening.

Biohybrid robotics

In the realm of biohybrid robotics, the DBG has pioneered "living machines" that bridge the gap between synthetic materials and biological actuation. Utilizing their expertise in muscular thin films, the group has developed autonomous biohybrid organisms, most notably a stingray-inspired robot in 2016 and a swimming fish in 2022, both powered by layers of living heart muscle cells. These robots are designed to respond to external cues, such as light, which triggers coordinated contractions in the cardiomyocyte layers to generate propulsion. In 2025, the group further optimized these designs by applying machine-learning directed optimization (ML-DO) to determine the most efficient fin geometries, resulting in biohybrid rays that swim twice as efficiently as previous biomimetic models. These projects serve as a proof-of-concept for creating complex, self-regulated biological systems that could eventually lead to autonomous medical probes or advanced prosthetic technologies.

Cardiovascular tissue engineering

The DBG's foundational work in cardiovascular tissue engineering focuses on the multiscale relationship between cellular architecture and organ function. By using bioprinting and textile-based manufacturing like Focused Rotary Jet Spinning (FRJS), the group has succeeded in fabricating 3D models of the human heart’s ventricles and complex vasculature. Their research delves into mechanotransduction, investigating how the extracellular matrix and cytoskeletal alignment influence the heart's electrophysiology and contribute to arrhythmias. This holistic approach—ranging from the nanoscale assembly of sarcomeres to the macroscale engineering of whole-heart geometries—seeks to provide a comprehensive understanding of both healthy cardiac development and the maladaptive remodeling that occurs in heart failure.  

Materials science and manufacturing,

Beyond medical applications, the group has made significant contributions to materials science and manufacturing, often drawing inspiration from biological structures to solve industrial and environmental challenges. Their work in nanofiber fabrication, particularly using Rotary Jet Spinning (RJS) and Immersion Rotary Jet Spinning (iRJS), has been repurposed to create high-performance materials such as bulletproof vests and extreme-temperature protective gear. To address global food waste, the lab developed a biodegradable, plant-based coating made of antimicrobial pullulan fibers that can be "shrink-wrapped" directly onto produce like avocados to extend their shelf life. This scalable, water-based spinning process replaces petroleum-based plastics with a non-toxic alternative that actively inhibits the growth of common pathogens like E. coli and Listeria. Furthermore, the group utilized iRJS to manufacture porous Kevlar nanofibers that combine high-strength ballistic protection with 20 times the thermal insulation of commercial gear, specifically designed for lightweight PPE for soldiers and first responders. Most recently, in 2025, they developed a "salt trick" to repurpose keratin from waste hair into eco-friendly bioplastics, providing a sustainable alternative to petroleum-based materials and demonstrating a closed-loop recycling process for protein-based polymers.

Cardiac Research

Our group’s primary research focus is on understanding cellular mechanotransduction in the heart. Specifically, we are interested in how extracellular matrix and cytoskeletal architecture potentiate and modulate the activation of mechanochemical and mechanoelectrical signaling pathways and genetic programs in cardiac cells and tissues. In order to study these mechanisms at different spatial scales, we use cellular and tissue engineering techniques that allow us to build custom-designed cardiac myocytes and ventricular tissue constructs as experimental preparations.

Why are we interested in this problem of biological scaling in the heart?

The Cardiac Arrhythmia Suppression Trial (CAST) of the late 1980’s was a clinical trial designed to test the hypothesis that suppression of premature ventricular contractions (PVC) with Class I antiarrhythmics (blockers of excitatory sodium currents) would reduce arrhythmic death risk. The trial was ended prematurely by the FDA when the mortality rate of those patients on encainide and flecainide, the Class I drugs studied, nearly quadrupled the mortality rates of those patients on placebo. Subsequent studies of antiarrhythmic drugs indicate that drugs that alter ion channel kinetics often show little or no benefit in the suppression of ventricular tachycardia and ventricular fibrillation. To date, there is no clinically reliable means of treating cardiac arrhythmias medicinally.

How are we approaching this problem?

We hypothesize that single channel blockade antiarrhythmic strategies were inherently flawed because they target a single scale (molecular level) without considering the fact that the pathogenesis of arrhythmias transcends multiple levels of integration, i.e., it is a multiscale problem. We propose that increasing the spatial scale of the drug target search, from single proteins to protein networks, will result in the development of more effective antiarrhythmic medicinal therapies. Thus, we take a multiscale approach, by targeting several spatial magnitudes simultaneously. At the length scale of a single cell, we study the cytoskeletal networks that span the entirety of the cardiac myocyte and modulate the kinetics of many of the more than half dozen ion channels that contribute to the cardiac action potential. More specifically, we investigate 1) how the cardiac myocyte cytoskeleton self-assembles; and, 2) the role of cytoskeletal architecture modulating action potential morphology and calcium metabolism. In tissue-scale studies, we investigate cell ensembles and correlate their behavior to larger tissue and whole heart function. Cell-cell mechanocoupling, via cell adhesion proteins and extracellular matrix, undoubtedly contributes to the electrical synchrony amongst cardiac myocytes. Here, more specific studies are directed towards investigating how the mechanical continuity amongst cardiac myocytes modulates electrical excitability and may contribute to the wavebreaks that mark the transition from ventricular tachycardia to ventricular fibrillation.

FIGURE: Microcontact Printing used to control Cardiomyocyte geometry and cellular architecture. For all Images: Sarcomeric actin labeled in green, sarcomeric alpha-actinin (Z-lines) marked in red, nucleus marked in blue.
A: Adult Rat Cardiac Myocyte without structural modification (nucleus not shown).
B: Neonatal Rat Cardiac Myocyte without structural modification, cultured on a monolayer of extracellular matrix protein.
C: Neonatal Rat Cardiac Myocyte cultured on a rectangular island of extracellular matrix protein.
D: Neonatal Rat Cardiac Myocyte cultured on a triangular island of extracellular matrix protein.
E: Neonatal Rat Cardiac Myocyte cultured on a square island of extracellular matrix protein.
F: Neonatal Rat Cardiac Myocyte cultured on a circular island of extracellular matrix protein.

Detection, Characterization and Visualization of Calcium Sparks In Micropatterned Cardiac Myocytes
Primary Investigator: Mark Bray, Ph.D.

The cytoarchitecture of the myocyte has been determined to be critical in understanding not only mechanical contraction of the cell but also electrical propagation. Knowledge of this mechanotransduction mechanism has implications in the treatment of stretch-activated arrhythmias, as well as understanding the role of the extracellular environment on intracellular signaling pathways. Our objective is to micropattern myocytes into various shapes and examine spark occurrence as a function of cell shape. The expectation is that cell shapes which incorporate regions of high mechanical cellular stress will modulate calcium spark characteristics as the cytoskeleton reconfigures itself accordingly. A critical and novel component of this project is the development of software able to detect and visualize sparks in two-dimensions.

FIGURE: Fluorescence map of square cell (top left) and with background fluorescence subtracted (bottom left). Visualization of spark boundaries with respect to (x,y,t), shown in red (right).

Estimation of Contractile Stress on Cardiac Myocytes
Primary Investigator: Poling Kuo, M.D.

We hypothesize that mechanical coupling between cells plays a critical role both in the normal and pathological development of cardiac tissues. We are using traction force microscopy to map the contractile stresses of micropatterned neonatal rat cardiomyocytes.

FIGURE: Relative stress field of cardiac myocytes exhibited by red vectors. The bottom black scale bar represents 10 um.