Nanometer-scale structure differences in the myofilament lattice spacing of two cockroach leg muscles correspond to their different functions

Abstract

Muscle is highly organized across multiple length scales. Consequently, small changes in the arrangement of myofilaments can influence macroscopic mechanical function. Two leg muscles of a cockroach have identical innervation, mass, twitch responses, length-tension curves and force-velocity relationships. However, during running, one muscle is dissipative (a 'brake'), while the other dissipates and produces significant positive mechanical work (bifunctional). Using time-resolved X-ray diffraction in intact, contracting muscle, we simultaneously measured the myofilament lattice spacing, packing structure and macroscopic force production of these muscles to test whether structural differences in the myofilament lattice might correspond to the muscles' different mechanical functions. While the packing patterns are the same, one muscle has 1 nm smaller lattice spacing at rest. Under isometric stimulation, the difference in lattice spacing disappeared, consistent with the two muscles' identical steady-state behavior. During periodic contractions, one muscle undergoes a 1 nm greater change in lattice spacing, which correlates with force. This is the first identified structural feature in the myofilament lattice of these two muscles that shares their whole-muscle dynamic differences and quasi-static similarities.

Mitochondrial Network Configuration Influences Sarcomere and Myosin Filament Structure in Striated Muscles

“…Within the A-band of the sarcomere, both actin and myosin are arranged in hexagonal lattice arrays where each myosin filament is surrounded by six other myosin filaments and also by six actin filaments which are closer to each myosin filament and form a smaller lattice 40,41 . Spacing within the myofilament lattices regulates sarcomere shortening velocity 42 , length-tension relationships 33 , cross-bridge kinetics 43,44 , and advective-diffusive metabolite transport 45 with as small as a 1 nm lattice spacing change correlating with force production 46 . Thus, to better understand the potential functional implications of heterogeneous myofilament structures within a given sarcomere, we determined whether the lattice spacing between myosin filaments was variable among different regions of the sarcomere.…”

“…Alterations in myofilament lattice spacing throughout the entire sarcomere are known to directly affect several measures related to force production (shortening velocity, length-tension relationships, cross-bridge kinetics, etc.) 41–46 . However, it remains unclear how variable lattice spacing within different regions of a single sarcomere influences force production.…”

Mitochondrial network configuration influences sarcomere and myosin filament structure in striated muscles

“…Alterations in myofilament lattice spacing throughout the entire sarcomere are known to directly affect several measures related to force production (shortening velocity, length-tension relationships, cross-bridge kinetics, etc.) [63][64][65][66][67][68] . However, it remains unclear how variable lattice spacing within different regions of a single sarcomere influences force production.…”

“…Within the A-band of the sarcomere, both actin and myosin are arranged in hexagonal lattice arrays where each myosin filament is surrounded by six other myosin filaments and also by six actin filaments which are closer to each myosin filament and form a smaller lattice 62,63 . Spacing within the myofilament lattices regulates sarcomere shortening velocity 64 , length-tension relationships 52 , cross-bridge kinetics 65,66 , and advectivediffusive metabolite transport 67 with as small as a 1 nm lattice spacing change correlating with force production 68 .…”

An optimized approach to study nanoscale sarcomere structure utilizing super-resolution microscopy with nanobodies

“…Sarcomeres are defined by their protein dense boundaries, known as Z-discs, and are otherwise largely composed of, actin, myosin, and titin proteins [5][6][7][8][9]. Numerous studies demonstrate that changes in the organization of these three major filamentous proteins affect the primary function of the sarcomere-to generate tension [6,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Further, although microscopic in size (~2.3-2.47 μm in total length), sarcomeres contain numerous additional proteins that localize to distinct domains that are important for its function [27].…”