Speaking from the Heart is Optics11 Life’s interview series with researchers at the forefront of muscle and cardiovascular science. In this episode of Speaking from the Heart, Dr. Giancarlo Forte from King’s College London discusses how cardiac mechanobiology and its modeling in engineered heart tissues can help researchers better understand heart disease.
The conversation explores how cells sense mechanical stress from extracellular matrix remodeling and cell-to-cell interactions, and how they translate these signals into biological responses. Giancarlo also discusses mechanosensitive pathways in the heart, including YAP/TAZ and force-regulated messenger RNA splicing, and how they influence cardiac pathologies such as fibrosis.
The episode also features how Optics11 Life’s Cuore platform supports research into engineered heart tissues by enabling researchers to study contractility, physiological parameters, tissue maturation, and disease-related changes in 3D cardiac models.
Watch the conversation here:
Dr. Giancarlo Forte
Dr. Giancarlo Forte is a Senior Lecturer in Cardiac Mechanobiology at King’s College London, within the British Heart Foundation Center of Excellence and the School of Cardiovascular and Metabolic Medicine and Sciences.
He obtained his Master’s degree in Biological Sciences from the University of Rome Tor Vergata, where he also completed his PhD in Experimental Pathophysiology. His career has included research positions in Germany, Italy, Japan, the Czech Republic, and the United Kingdom.
Before joining King’s College London, Dr. Forte worked at the International Clinical Research Center of St. Anne’s University Hospital in Brno, where he founded the Center for Translational Medicine and led the Mechanobiology of Disease Group.
His research combines induced pluripotent stem cells, 3D advanced disease models, imaging, molecular biology, and bioengineering to study how biomechanical stress and extracellular matrix remodeling influence mechanosensitive DNA transcription, RNA metabolism, and cardiovascular disease.
Why watch this interview?
The heart is a highly mechanical organ. It is continuously exposed to passive mechanical stress, while also producing active forces through contraction. This makes mechanobiology central to understanding how cardiac cells function, adapt, and change during disease.
In this interview, Giancarlo explains how his group combines molecular biology, bioengineering, human-induced pluripotent stem cells, 3D culture systems, organoids, and engineered heart tissues to study cardiovascular disease.
A key theme is how changes in the extracellular matrix can influence cardiomyocyte function, mechanosensitive signaling, nuclear integrity, gene expression, and RNA biology. The discussion connects fundamental mechanobiology with clinically relevant questions in cardiac fibrosis, heart failure, and the development of more advanced human disease models.
Why is mechanobiology important in cardiac disease research?
Cardiac cells are constantly exposed to mechanical stress. In the heart, changes in the structure, mechanics, and function of the extracellular matrix can influence how cells sense their environment and respond at the molecular level.
Mechanobiology helps researchers study these processes by connecting physical cues, such as stiffness, compression, tension, and matrix remodeling, with biological outcomes such as adhesion, gene expression, RNA metabolism, contractility, and tissue function.
In the interview, Giancarlo explains that mechanically activated pathways may be important for designing new interventions for cardiovascular diseases.
How are engineered heart tissues used in this research?
Giancarlo’s group uses 3D cardiac models, including engineered heart tissues, to reproduce aspects of heart muscle complexity in vitro.
In these models, cardiac cells are embedded in hydrogels and cast as muscle bundles between two pillars. This setup lets researchers study contractility and contraction-related physiological parameters. Compared with 2D cultures, engineered heart tissues support cardiomyocyte alignment, bundle formation, cell-to-cell interaction, and changes in calcium transmission.
These models help researchers study how mechanosensitive pathways contribute to muscle formation, muscle function, and cardiac disease.
What role does the extracellular matrix play in Giancarlo’s research?
A central focus of the interview is the extracellular matrix’s role in cardiac fibrosis.
Giancarlo describes how his group creates a fibrotic decellularized matrix from human induced pluripotent stem cell-derived cardiac fibroblasts. They can then use this matrix in engineered heart tissues to study how fibrotic cues affect cardiomyocyte function.
This approach allows researchers to investigate how extracellular matrix remodeling after cardiac injury may influence the mechanical environment of heart cells, including sarcomere structure, nuclear shape, chromatin accessibility, gene expression, and cardiac function.
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