Critical dependence of calcium-activated force on width in highly compressed skinned fibers of the frog.

Force development by skinned frog semitendinosus fibers was studied at various levels of lateral compression to compare the results with intact fibers and to evaluate the limits on cross-bridge movements during isometric contraction. The skinned fibers were compressed osmotically using a high molecular weight polymer, dextran T500. Ca-activated force remained constant down to 58% of the fiber width (w0) after skinning, corresponding to a nearly twofold change in separation between the thin and thick filaments in the myofilament lattice. This agrees with the earlier result on intact fibers, and gives additional evidence that the cross-bridge mechanism for force generation is relatively insensitive to large changes in interfilament separation. Further compression, below 0.58 w0, produced a sharp drop in force, and the force was practically zero at a fiber width of 50%. The effect at high compression was the same at all pCa's, which indicates that the Ca sensitivity of the myofilaments is unaffected by radial compression. The stiffness of the fiber remained high in rigor in the presence of dextran, which indicates that the rigor cross-bridge attachment is not inhibited, and actually may be improved, with decreases in the interfilament space. Also, the drop in active force with the highest compression was similar when the compressed fibers were put in rigor before contraction, which suggests that the force drop also was not due to a hindrance to cross-bridge attachment. The results appear to exclude large motions such as tilting and rocking of the bridge as a rigid molecule, but suggest that at least some molecular movement is essential for force development; they also raise the possibility that there is a critical interfilament separation in the fiber, below which the cross-bridge cannot function.