With every heartbeat, the cells in the heart are subjected to a cycle of stretching and contraction. Within this dynamic mechanical environment, cardiac myocytes, the primary functional cells of the heart, must generate the precise forces necessary to pump blood to the rest of the body. These forces arise from highly organized and tightly controlled interactions between actin and myosin filaments. Notably, the myocyte’s contractile force depends on the degree of actin-myosin overlap, and the overlap depends on the deformation of the myocyte. A better understanding of the relationship between myocyte deformation and force generation has the potential to improve predictive models of disease progression and inform therapeutic decision making.
In our recent study, featured on the cover of the September 2, 2025 issue of Biophysical Journal, we explored the mechanical behavior of single cardiac myocytes exposed to complex loads. The cover image depicts a single mouse cardiomyocyte micropatterned into an in vivo–like geometry and labeled with a fluorescent, cell-permeable probe for F-actin. From top to bottom, the image shows the cell at increasing levels of stretch. The dark vertical lines within the fibers delineate the border between sarcomeres, the basic contractile units of striated muscle. As the cell is stretched, the spacing between the sarcomeres elongates.
It is well established that the contractile force generated by striated muscle is correlated with the sarcomere spacing. Using a combination of fluorescent imaging and single-cell force measurements, we found that cardiac myocytes stretched parallel to their long axes, as shown in the image, have the same length-force relationship seen in cardiac tissue. However, this relationship did not hold true when non-axial stretch is considered. Using a simple computational model, we postulate that the sarcomere length and the sarcomere lattice spacing act together to determine how deformation affects myocyte force generation. These results have important implications in cardiac physiology, particularly for how we might think about cardiomyocyte function in non-idealized mechanical conditions.
Our group is interested in the mechanical behavior of cells, with a focus on understanding how cells sense and adapt to changes in their mechanical environment, which is essential to both healthy development and disease progression. Our ultimate goal is to develop physiologically relevant models of mechanoadaptation to improve understanding of tissue functionality and inform therapeutic strategies. More information about the Alford Lab’s research can be found at https://cse.umn.edu/research/alford.
— Taylor M. Rothermel, Houda Cohen, Anna Grosberg, Joseph M. Metzger, and Patrick W. Alford