Meeting Abstract

6.4  Wednesday, Jan. 4  Pulling apart lattice spacing: interfilament distance regulates force WILLIAMS, C.D.*; SALCEDO, M. K.; REGNIER, M.; IRVING, T. C.; DANIEL, T. L.; Univ. of Washington, Seattle; Univ. of Washington, Seattle; Univ. of Washington, Seattle; Ill. Inst. of Technology, Chicago; Univ. of Washington, Seattle

As muscle contracts it both shortens and grows thicker. Under isovolumetric conditions the increase in thickness spreads the contractile lattice of the muscle cell. This spread changes the orientation of muscle's molecular motors relative to the sites where they may bind and produce force. Our previous models show that lattice spacing strongly modulates the maximum isometric force muscle can generate. Lattice spacing's influence is on the same order of magnitude as that exerted by the change in the overlap between the contractile filaments that occurs during shortening. Here we use measurements of force in muscle whose lattice spacing we osmotically control and monitor through x-ray diffraction imaging to examine the interaction between lattice spacing and force in skinned muscle fibers. D10 lattice spacing varies between 40 and 60 nm and has a significant (p=0.006) 0.4 correlation with maximum force. Initial lattice spacing prior to a given contraction is offset by the introduction of a high molecular weight sugar into the relaxing and activating solutions, Force and lattice spacing data were collected simultaneously by means of an automated apparatus developed for the task. Our x-ray diffraction derived measurements support the results of our prior models, showing a non-sarcomere-length dependence to the maximum isometric force generated. Combined with new modeling results, these data suggest that much of the increased force seen in the ascending limb of the sarcomere length-tension relationship is due to changes in lattice spacing, rather than changes in filament overlap.