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Mechanical Forces Accelerate Collagen Digestion by Bacterial Collagenase in Lung Tissue Strips.

Yi E, Sato S, Takahashi A, Parameswaran H, Blute TA, Bartolák-Suki E, Suki B - Front Physiol (2016)

Bottom Line: Most tissues in the body are under mechanical tension, and while enzymes mediate many cellular and extracellular processes, the effects of mechanical forces on enzyme reactions in the native extracellular matrix (ECM) are not fully understood.Generally, mechanical loading increased the effects of enzyme activity characterized by an irreversible decline in stiffness and tissue deterioration seen on both confocal and electron microscopic images.These results suggest that the decline in stiffness results from rupture of collagen followed by load transfer and subsequent rupture of alveolar walls.

View Article: PubMed Central - PubMed

Affiliation: Cell and Tissue Mechanics, Department of Biomedical Engineering, Boston University Boston, MA, USA.

ABSTRACT
Most tissues in the body are under mechanical tension, and while enzymes mediate many cellular and extracellular processes, the effects of mechanical forces on enzyme reactions in the native extracellular matrix (ECM) are not fully understood. We hypothesized that physiological levels of mechanical forces are capable of modifying the activity of collagenase, a key remodeling enzyme of the ECM. To test this, lung tissue Young's modulus and a nonlinearity index characterizing the shape of the stress-strain curve were measured in the presence of bacterial collagenase under static uniaxial strain of 0, 20, 40, and 80%, as well as during cyclic mechanical loading with strain amplitudes of ±10 or ±20% superimposed on 40% static strain, and frequencies of 0.1 or 1 Hz. Confocal and electron microscopy was used to determine and quantify changes in ECM structure. Generally, mechanical loading increased the effects of enzyme activity characterized by an irreversible decline in stiffness and tissue deterioration seen on both confocal and electron microscopic images. However, a static strain of 20% provided protection against digestion compared to both higher and lower strains. The decline in stiffness during digestion positively correlated with the increase in equivalent alveolar diameters and negatively correlated with the nonlinearity index. These results suggest that the decline in stiffness results from rupture of collagen followed by load transfer and subsequent rupture of alveolar walls. This study may provide new understanding of the role of collagen degradation in general tissue remodeling and disease progression.

No MeSH data available.


Related in: MedlinePlus

Examples of confocal images of the alveolar structure in lung tissue strips following 60 min of one of the conditions: no stretch and no digestion (A), no stretch and digestion (B), 40% strain no digestion (C), 40% strain digestion (D), 80% strain and digestion (E), and 20% dynamic strain superimposed on 40% static strain at 1 Hz (F). The bar represents 100 μm. In all cases, imaging was done in the unstretched state.
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Figure 6: Examples of confocal images of the alveolar structure in lung tissue strips following 60 min of one of the conditions: no stretch and no digestion (A), no stretch and digestion (B), 40% strain no digestion (C), 40% strain digestion (D), 80% strain and digestion (E), and 20% dynamic strain superimposed on 40% static strain at 1 Hz (F). The bar represents 100 μm. In all cases, imaging was done in the unstretched state.

Mentions: To assess the structural changes in the parenchyma, confocal images of the alveolar wall network were obtained for selected groups including C0%, C40%, C40%d (control samples at 40% static stretch and superimposed dynamic stretch at 20% amplitude at 1 Hz), D0%, D20%, D40%, D80%, and D40%d = 20%,1. Example images are summarized in Figure 6 and statistical analysis of the structure is shown in Figure 7. The equivalent diameters (Figure 7A) in the undigested C40% and C40%d groups were smaller than all digested groups (p < 0.001) with the exception that D20% was not different from C40%d. The equivalent diameter of the C40%d group was also statistically significantly higher than that of C40%. We also examined the heterogeneity of the airspace structure by comparing the variance of equivalent diameters in Figure 7B. The heterogeneity was the smallest in the C40% group and this was statistically significantly smaller than the heterogeneity of all other groups. The D40%, D40%d, and D80% groups were not different from each other, but they were higher than the remaining groups. Additionally, the C40%d group showed higher heterogeneity than the D0% group. Interestingly, the percent drop in Y showed a strong correlation with airspace heterogeneity (Figure 7C) with an r2 of 0.844 (p = 0.01). The distortion index (Figure 7D) was higher in the C40%d group than in the D80% and D40%d groups (p < 0.001).


Mechanical Forces Accelerate Collagen Digestion by Bacterial Collagenase in Lung Tissue Strips.

Yi E, Sato S, Takahashi A, Parameswaran H, Blute TA, Bartolák-Suki E, Suki B - Front Physiol (2016)

Examples of confocal images of the alveolar structure in lung tissue strips following 60 min of one of the conditions: no stretch and no digestion (A), no stretch and digestion (B), 40% strain no digestion (C), 40% strain digestion (D), 80% strain and digestion (E), and 20% dynamic strain superimposed on 40% static strain at 1 Hz (F). The bar represents 100 μm. In all cases, imaging was done in the unstretched state.
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Related In: Results  -  Collection

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Figure 6: Examples of confocal images of the alveolar structure in lung tissue strips following 60 min of one of the conditions: no stretch and no digestion (A), no stretch and digestion (B), 40% strain no digestion (C), 40% strain digestion (D), 80% strain and digestion (E), and 20% dynamic strain superimposed on 40% static strain at 1 Hz (F). The bar represents 100 μm. In all cases, imaging was done in the unstretched state.
Mentions: To assess the structural changes in the parenchyma, confocal images of the alveolar wall network were obtained for selected groups including C0%, C40%, C40%d (control samples at 40% static stretch and superimposed dynamic stretch at 20% amplitude at 1 Hz), D0%, D20%, D40%, D80%, and D40%d = 20%,1. Example images are summarized in Figure 6 and statistical analysis of the structure is shown in Figure 7. The equivalent diameters (Figure 7A) in the undigested C40% and C40%d groups were smaller than all digested groups (p < 0.001) with the exception that D20% was not different from C40%d. The equivalent diameter of the C40%d group was also statistically significantly higher than that of C40%. We also examined the heterogeneity of the airspace structure by comparing the variance of equivalent diameters in Figure 7B. The heterogeneity was the smallest in the C40% group and this was statistically significantly smaller than the heterogeneity of all other groups. The D40%, D40%d, and D80% groups were not different from each other, but they were higher than the remaining groups. Additionally, the C40%d group showed higher heterogeneity than the D0% group. Interestingly, the percent drop in Y showed a strong correlation with airspace heterogeneity (Figure 7C) with an r2 of 0.844 (p = 0.01). The distortion index (Figure 7D) was higher in the C40%d group than in the D80% and D40%d groups (p < 0.001).

Bottom Line: Most tissues in the body are under mechanical tension, and while enzymes mediate many cellular and extracellular processes, the effects of mechanical forces on enzyme reactions in the native extracellular matrix (ECM) are not fully understood.Generally, mechanical loading increased the effects of enzyme activity characterized by an irreversible decline in stiffness and tissue deterioration seen on both confocal and electron microscopic images.These results suggest that the decline in stiffness results from rupture of collagen followed by load transfer and subsequent rupture of alveolar walls.

View Article: PubMed Central - PubMed

Affiliation: Cell and Tissue Mechanics, Department of Biomedical Engineering, Boston University Boston, MA, USA.

ABSTRACT
Most tissues in the body are under mechanical tension, and while enzymes mediate many cellular and extracellular processes, the effects of mechanical forces on enzyme reactions in the native extracellular matrix (ECM) are not fully understood. We hypothesized that physiological levels of mechanical forces are capable of modifying the activity of collagenase, a key remodeling enzyme of the ECM. To test this, lung tissue Young's modulus and a nonlinearity index characterizing the shape of the stress-strain curve were measured in the presence of bacterial collagenase under static uniaxial strain of 0, 20, 40, and 80%, as well as during cyclic mechanical loading with strain amplitudes of ±10 or ±20% superimposed on 40% static strain, and frequencies of 0.1 or 1 Hz. Confocal and electron microscopy was used to determine and quantify changes in ECM structure. Generally, mechanical loading increased the effects of enzyme activity characterized by an irreversible decline in stiffness and tissue deterioration seen on both confocal and electron microscopic images. However, a static strain of 20% provided protection against digestion compared to both higher and lower strains. The decline in stiffness during digestion positively correlated with the increase in equivalent alveolar diameters and negatively correlated with the nonlinearity index. These results suggest that the decline in stiffness results from rupture of collagen followed by load transfer and subsequent rupture of alveolar walls. This study may provide new understanding of the role of collagen degradation in general tissue remodeling and disease progression.

No MeSH data available.


Related in: MedlinePlus