MUSCLE THICK FILAMENTS ARE RIGID COUPLED TUBULES, NOT FLEXIBLE ROPES

Understanding the structures of thick filaments and their relation to muscle contraction has been an important problem in muscle biology. Th e flexural rigidity of natural thick filaments isolated from Caenorhab ditis elegans as determined by statistical analysis of their electron microscopic images shows that they are considerably more rigid (persis tence length = 263 mu m) than similarly analyzed synthetic actin filam ents (6 mu m) or duplex DNA (0.05 mu m), which are known to be helical ropes. Indeed, cores of C. elegans thick filaments, having only 11% o f the mass per unit length of intact thick filaments, are quite rigid (85 mu m) compared with the thick filaments. Cores comprise the backbo nes of the thick filaments and are composed of tubules containing seve n subfilaments cross-linked by non-myosin proteins. Microtubules recon stituted from rubulin and microtubule-associated proteins are nearly a s rigid (55 mu m) as the cores. We propose a model of coupled tubules as the structural basis for the observed rigidity of natural thick fil aments and other linear structures such as microtubules. A similar mod el was recently presented for microtubules [Felgner et al., 1997]. Thi s coupled tubule model may also explain the differences in flexural ri gidity between natural rabbit skeletal muscle thick filaments (27 mu m ) or synthetic thick filaments reconstituted from myosin and myosin bi nding protein C (36 mu m) and those reconstituted from purified myosin (9 mu m). The more flexible myosin structures may be helical ropes li ke F-actin or DNA, whereas the more rigid muscle or synthetic thick fi laments which contain myosin and myosin binding protein C may be const ructed of subfilaments coupled into tubules as in C. elegans cores. Th e observed thick filament rigidity is necessary for the incompressibil ity and lack of flexure observed with thick filaments in contracting s keletal muscle. Cell Motil. Cytoskeleton 41:195-201, 1998. (C) 1998 Wi ley-Liss, Inc.