Biaxial length-tension relationship in single cardiac myocytes

The length-tension relationship is an important principle in striated muscle biomechanics that relates the contractile force generation to Z-disk spacing within the sarcomere. The resulting bell-shaped curve is traditionally understood to be principally related to the actin-myosin overlap within the sarcomere. Here, we use cellular microbiaxial stretching (CμBS) methods to study how the deformation of single micropatterned neonatal mouse cardiac myocytes influences their contractile function and develop a biaxial length-tension relationship. We find that when the cells are stretched parallel to their long axes, CμBS studies replicate the bell-shaped curve typical of isolated muscle studies. We further found that when the myocytes are stretched parallel to their short axes, a similar bell-shaped curve is observed; however, the relationship between Z-disk spacing and force does not align with the axial observations. We then present a model that considers the effects of both actin-myosin overlap and sarcomere lattice spacing on optimal myosin head working length, which is able to capture the experimentally observed forces. This work adds to the current understanding of the mechanical behavior of cardiac myocytes, leading to a better understanding of the interplay between sarcomere length, lattice spacing, and active force generation in cardiac muscle.