02), with a correlation coefficient (R-value) of 0.67 (R2 of 0.45). The forces are graphed versus myotube CSA in Figure Figure33. Figure 3 Force generated by individual myotubes correlated with the myotube
CSA (R2=0.45), which was selected as the sole predictor for force by multiple regression analysis. Force values presented were calculated using the FEA approach. After normalizing the force data to the CSA, the coefficient of variance was greatly reduced versus the non-normalized data. The force normalized to CSA is by Inhibitors,research,lifescience,medical definition the stress in the myotube along the longitudinal axis. Normalizing the force to CSA decreased the COV by 14% and 19%, using the data from the Stoney’s equation and FEA approaches, respectively. The signal-to-noise Inhibitors,research,lifescience,medical ratio—the inverse of the COV—changed more dramatically, with the area-normalized force exhibiting a 17% and 23% higher signal-to-noise ratios than the non-normalized force using the two methods. The use of cantilevers to determine stresses generated in a thin film on a cantilever beam is a well-established and understood field of physics, and we have shown it can be an adaptive solution to the technological need for stress measurement in biological tissues at the microscale.23, Inhibitors,research,lifescience,medical 24 The integration of muscle mechanics with silicon device mechanics and transduction now establish a controlled, predictable assay system, and the ability
to model the hybrid system selleck Imatinib further allows a better understanding of the mechanisms for many applications in biotechnology. A direct correlation between myotube physical attributes and force production in vitro, as demonstrated here, is a significant Inhibitors,research,lifescience,medical finding, since it suggests the developed model closely parallels the functional characteristics of the native tissue, where muscle Inhibitors,research,lifescience,medical size, specifically cross-sectional area, has been shown to be directly linked to force production.13, 14, 15 This bioMEMS device can now be transitioned into a system for the study of muscle sellckchem physiology and muscle-related diseases for human drug discovery
applications. From a physiological perspective, the conclusion that myotube force generation scales with CSA validates that the in vitro data collected from the cantilever bioMEMS device matches the in vivo data trends.13, 25 The regression analysis AV-951 sufficiently establishes that the CSA of a myotube is important in dictating its force generation capability. However, the fact that roughly 50% of the variation in the force values was not explained by the CSA indicates that this factor is not the sole determinant of myotube contractile force in this system. Reports correlating muscle strength to physical parameters in vivo demonstrated that the CSA is the best predictor of strength among the variables tested.13, 14, 15 However, the in vivo strength data did not follow CSA exactly, with the R value roughly 0.5 (R2≈0.
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