Fine structure of wide and narrow vertebrate muscle Z-lines: A proposed model and computer simulation of Z-line architecture

Abstract

A model of the structure of vertebrate Z-lines and Z-line analogs is introduced and supported by evidence from electron microscope studies of wide Z-lines (rat and feline soleus, and feline and canine cardiac muscles), narrow Z-lines (guppy, newt and frog skeletal muscles), and Z-rods (from a patient with nemaline myopathy and from cardiac muscles of aged dog). The model is based on a pair of Z-filaments (termed a Z-unit), which are linked near their centers at a 90 ° angle and form bridges between neighboring antipolar thin (actin) filaments. A square lattice of four Z-filament pairs (the basic structure of the Z-line, termed a Z-line unit) defines the geometrical position of the I-square unit. In this native state of the Z-line, small square and large square net forms appear in cross-section. Other cross-sectional patterns of Z-lines, including basket-weave and diagonal-square net patterns, can be explained by detachment of the Z-filament from the Z-filament binding region within each Z-filament pair due to chemical or physical stress. Dissection of Z-lines and Z-line analogs with calcium-activated neutral protease provides evidence that the width of all wide Z-line structures is determined by the amount of overlap of antipolar thin filaments from adjacent sarcomeres. Longitudinal patterns of narrow and wide Z-lines are shown and described in relation to the model. To test the proposed model, the dynamics of the Z-line unit structure were computer-simulated. An attempt was made to correlate longitudinal ( z direction) and cross-sectional ( x and y directions) patterns and to determine the amount of movement of thin or Z-filaments that is required to explain the diversity observed in cross-sectional patterns of Z-lines. The computer simulations demonstrated that the structural transitions among the small square, and therefore large square net, as well as basket-weave and diagonal-square net forms seen in cross-sections could be caused by movements of thin filaments less than 10 nm in any direction ( x, y or z). Under the assumptions of Z-filament length equal to 30 nm and thin filament square nets having 22 nm long sides, the transition from the small square form (minimum Z-line unit width, 20·4 nm in the case of narrow fish Z-lines) to the diagonal-square form (maximum Z-line unit width, 25·7 nm in the case of narrow fish Z-lines) could be obtained with a total shift of the thin filaments of only 5·3 nm toward the α-bands ( z direction), without expansion of the thin filament square net ( x and y directions). If it is assumed that the adjacent antipolar thin filaments at the Z-line move in opposite directions toward their respective A-bands, the amount of the shift of thin filaments on one side of the Z-line would be only 2·65 nm. This small total shift of thin filaments also is applicable to wide Z-lines during structural transitions. The small shifts needed can explain why basket-weave forms are sometimes observed in electron micrographs that show no detectable evidence of thin filament disturbance in cross-section. The small shift in the z direction also probably explains how the network of Z-filaments, each bound to two antipolar thin filaments, (1) can originally form 90 ° angles in cross-section and determine the native structure of thin filament square nets in the small square (and large square) form; (2) can realign into the basket-weave form having a clockwise and counterclockwise configuration in which the Z-filaments form a pattern with 45 ° angles offset from thin filament square nets; and (3) can change from the somewhat curved, tangential appearance of Z-filaments in the basket-weave form to regain their straightness while maintaining the 45 ° angle offset from the thin-filament square net in the diagonal square net pattern.