Communicating stress to cell nuclei in cardiomyocytes

The nucleus of a cardiomyocyte, the heart muscle cell, serves as the command center for gene transcription, enabling the heart to adapt to stress and fluctuating hemodynamic demands. Despite its importance, the mechanisms by which stress signals travel from the cellular environment to the nucleusand how these signals shape gene activity to improve or impair the heart`s contractile functionremain poorly understood. This knowledge gap is especially critical in distinguishing how physiological stress, such as exercise, enhances cardiac performance versus how pathological stress can lead to disease. Cardiomyocytes are unique among cells due to their highly specialized structure, electrical excitability, and constant exposure to rhythmic contractile forces. These features demand precise communication between external stressors and the nucleus to maintain proper function. Our research will explore how cardiomyocyte nuclei respond to environmental triggers, including neurohormonal, metabolic, and mechanical signals, each having distinct impacts on overall cellular function based on their interplay. Specifically, our study aims to uncover how these stressors alter local signaling and mechanical forces around the nucleus, driving changes in the transcriptomethe set of active genes that determine contractile function. Using cutting-edge 3D electron microscopy and live imaging, we will analyze how the nucleus moves and responds under physiological conditions (like exercise) and pathological states. By linking nuclear mechanics to changes in the transcriptomic landscape, we hope to provide a comprehensive understanding of how the heart adaptsor maladaptsto stress. This work has the potential to reveal the molecular basis of the hearts beneficial adaptation to exercise while identifying early, treatable mechanisms underlying adverse cardiac remodeling in diseases. Such insights could pave the way for novel therapeutic approaches to improve heart health and combat heart failure.