Rothermel Taylor M, Cohen Houda, Grosberg Anna, Metzger Joseph M, Alford Patrick W
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota.
Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota.
Biophys J. 2025 Sep 2;124(17):2865-2876. doi: 10.1016/j.bpj.2025.07.028. Epub 2025 Jul 28.
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.
长度-张力关系是横纹肌生物力学中的一个重要原理，它将收缩力的产生与肌节内Z盘间距联系起来。传统上认为，由此产生的钟形曲线主要与肌节内肌动蛋白-肌球蛋白的重叠有关。在这里，我们使用细胞微双轴拉伸（CμBS）方法来研究单个微图案化新生小鼠心肌细胞的变形如何影响其收缩功能，并建立双轴长度-张力关系。我们发现，当细胞沿其长轴方向拉伸时，CμBS研究重现了孤立肌肉研究中典型的钟形曲线。我们还进一步发现，当心肌细胞沿其短轴方向拉伸时，也观察到类似的钟形曲线；然而，Z盘间距与力之间的关系与轴向观察结果不一致。然后，我们提出了一个模型，该模型考虑了肌动蛋白-肌球蛋白重叠和肌节晶格间距对最佳肌球蛋白头部工作长度的影响，能够捕捉实验观察到的力。这项工作增进了我们目前对心肌细胞力学行为的理解，有助于更好地理解心肌中肌节长度、晶格间距和主动力产生之间的相互作用。
