Abstract
Length changes of muscle fibers have previously been shown to result in a temporary reduction in fiber stiffness that is referred to as thixotropy. Understanding the mechanism of this thixotropy is important to our understanding of muscle function since there are many instances in which muscle is subjected to repeated patterns of lengthening and shortening. By applying sinusoidal length changes to one end of single permeabilized muscle fibers and measuring the force response at the opposite end, we studied the history-dependent stiffness of both relaxed and activated muscle fibers. For length change oscillations greater than 1 Hz, we observed thixotropic behavior of activated fibers. Treatment of these fibers with EDTA and blebbistatin, which inhibits myosin-actin interactions, quashed this effect, suggesting that the mechanism of muscle fiber thixotropy is cross-bridge dependent. We modeled a half-sarcomere experiencing sinusoidal length changes, and our simulations suggest that thixotropy could arise from force-dependent cross-bridge kinetics. Surprisingly, we also observed that, for length change oscillations less than 1 Hz, the muscle fiber exhibited rheopexy. In other words, the stiffness of the fiber increased in response to the length changes. Blebbistatin and EDTA did not disrupt the rheopectic behavior, suggesting that a non-cross-bridge mechanism contributes to this phenomenon.
Highlights
Certain non-Newtonian fluids exhibit a time-dependent change in viscosity when they experience shear stress
Individual muscle fibers were subjected to sinusoidal length changes at one end at frequencies ranging from 0.25 to 30 Hz, and the resulting force response was measured at the other end of the fiber
Intact fiber measurements of relaxed muscle fibers indicate that thixotropy in muscle arises from a history dependent, short-range elastic component (SREC) [14,15,16], the nature of the SREC is still debated
Summary
Certain non-Newtonian fluids exhibit a time-dependent change in viscosity when they experience shear stress. When the viscosity of the fluid is reduced by shear stress, the material is said to exhibit thixotropy, and when shear stress increases the fluid’s viscosity, it is said to exhibit rheopexy [1]. Both phenomena typically result from reversible changes in microstructure. Buchtal and Kaiser [2] first used the term thixotropy to describe their observations that stretching an amphibian skeletal muscle fiber results in reduced fiber stiffness, and that the stiffness returns to its unperturbed value after a sufficient resting period.
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