Tissue homeostasis reflects a balance of synthesis and degradation, and past studies of homogeneously stressed tissues and collagen materials indicate collagen degradation is suppressed by strain. Such processes are studied here in isolated tendons and in beating embryonic hearts. Collagen fibrils in tendon fascicles orient along the tension axis, but heterogeneous strains and gradients were induced using three-point bending plus adhesion, with patterned photo-bleaching of a fluorescent fascicles used to measure strain. Tissue microstructure was simultaneously imaged using Second Harmonic Generation (SHG) signal while deformed fascicle samples were exposed to purified Matrix Metalloproteinase-1 (MMP-1) or Bacterial collagenase (BC). Within physiological strain limits (i.e. ∼5-8%), the decrease in degradation rate (relative to strain-free) was nearly independent of collagenase type despite different cleavage mechanisms, whereas tissue locations sustaining higher strains showed the degradation rate became almost independent of strain magnitudes. The dependence of degradation rate on mechanical strain suggests a sequestration of collagen's cleavage sites, which we posit because permeation and mobility of fluorescent collagenase and dextran are strain-independent up to ∼5-8% strains. Normal beating hearts are also subjected to ∼5% peak strain in a spatiotemporally coordinate contractile wave, and the hearts maintain collagen mass until strain is suppressed by inhibition of myosin-II. Endogenous MMPs then degrade the collagens in 30-60 min based on addition or not of MMP inhibitors and quantitation by calibrated mass spectrometry. Both tissue systems under heterogeneous strains indicate a degradative sculpting of tissue locations that sustain the lowest strains.