Electron microscopy of cardiac 3D nanodynamics: form, function, future

In this Review, the authors discuss the latest insight into the 3D nanostructure of the heart and how deformation during contraction and relaxation affects cellular function. They also describe technological breakthroughs in biological sample preparation, 3D imaging and data analysis with electron microscopy. The 3D nanostructure of the heart, its dynamic deformation during cycles of contraction and relaxation, and the effects of this deformation on cell function remain largely uncharted territory. Over the past decade, the first inroads have been made towards 3D reconstruction of heart cells, with a native resolution of around 1 nm(3), and of individual molecules relevant to heart function at a near-atomic scale. These advances have provided access to a new generation of data and have driven the development of increasingly smart, artificial intelligence-based, deep-learning image-analysis algorithms. By high-pressure freezing of cardiomyocytes with millisecond accuracy after initiation of an action potential, pseudodynamic snapshots of contraction-induced deformation of intracellular organelles can now be captured. In combination with functional studies, such as fluorescence imaging, exciting insights into cardiac autoregulatory processes at nano-to-micro scales are starting to emerge. In this Review, we discuss the progress in this fascinating new field to highlight the fundamental scientific insight that has emerged, based on technological breakthroughs in biological sample preparation, 3D imaging and data analysis; to illustrate the potential clinical relevance of understanding 3D cardiac nanodynamics; and to predict further progress that we can reasonably expect to see over the next 10 years.

Automated summary

This Review discusses the latest insight into the 3D nanostructure of the heart and its impact on cellular function during contraction and relaxation. Technological breakthroughs in biological sample preparation, 3D imaging, and data analysis have provided access to new data and driven the development of smart image-analysis algorithms. The authors highlight the scientific discovery and potential clinical relevance of understanding 3D cardiac nanodynamics, as well as predict further progress in the next decade.