Abstract
Mechanical forces play a significant role during the organogenesis of striated muscle. The rapid bone elongation in the limb and the marked increases in blood pressure and volume during development help to organize skeletal myofibers and cardiomyocytes, respectively, into the proper three-dimensional cellular pattern necessary for a functional organ. The mechanotransduction processes regulating organogenesis can be studied in tissue culture by growing isolated embryonic cells on an elastic substratum and repetitively loading the substratum with computer controlled stepper motors. Both avian skeletal muscle and rodent cardiac muscle cells have been mechanically loaded while undergoing differentiation in vitro by patterns of activity that simulate the in vivo environment. In the presence of appropriate exogenous growth factors and extracellular matrix molecules, mechanical stimulation leads to the growth and organization of these cells into 2- and 3-dimensional organ-like structures (“organoids”) (Vandenburgh and Karlisch, 1989; Vandenburgh et al., 1991; Vandenburgh et al., 1995b). These organoids display many morphological characteristics of in vivo organs including skeletal myofibers organized into fascicles with developing tendon-like structures (Fig. 1), and sheets of parallel, interconnected rod-shaped cardiomyocytes. The pattern of unidirectional and repetitive mechanical stimulation is critical for the proper in vivo-like arrangement of the cells. For example, unidirectional stretching without relaxation of both skeletal and cardiac muscle cells aligns them in the direction of stretch, while repetitive stretch-relaxation of the same cells causes them to align perpendicular to the direction of stretch. Percent cell stretch and frequency of stretch are also important parameters in determining the growth response of the cells to mechanical forces.
