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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

Top row: Network images under simulated conditions of no enzyme and static 40% strain (A), enzyme and no stretched (B), and enzyme and static 40% strain allowing breaking (C). Color is proportional to force (color bar below B) increasing from blue to red. Note the increased degradation and heterogeneity in structure in (C). Note also that in (B) colors are bluish representing less force due to weakening of springs whereas in (C) colors are similar to those in (A) despite weakening of springs. This is due to load transfer following breaking. (D,F) shows selected time courses of experimentally obtained normalized Young's moduli (Y) and normalized nonlinearity index k. (E,G) shows normalized Y and k from the network model demonstrating a good correspondence with the experimental data.
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Figure 9: Top row: Network images under simulated conditions of no enzyme and static 40% strain (A), enzyme and no stretched (B), and enzyme and static 40% strain allowing breaking (C). Color is proportional to force (color bar below B) increasing from blue to red. Note the increased degradation and heterogeneity in structure in (C). Note also that in (B) colors are bluish representing less force due to weakening of springs whereas in (C) colors are similar to those in (A) despite weakening of springs. This is due to load transfer following breaking. (D,F) shows selected time courses of experimentally obtained normalized Young's moduli (Y) and normalized nonlinearity index k. (E,G) shows normalized Y and k from the network model demonstrating a good correspondence with the experimental data.

Mentions: Figure 9 shows example configurations of the network model before (Figure 9A) and after digestion in the absence (Figure 9B) and presence (Figure 9C) of stretch. The stiffness of the networks was calculated at 15 and 36% strains along the stress-strain curve similarly to the experimental data. The normalized stiffness and nonlinearity index are compared to the corresponding experimental results in Figures 9D–G. It can be seen that the network model matches the trends seen in the experimental data well. The network image in Figure 9C also displays a similar pattern of airspace enlargement seen in the confocal images in Figure 6.


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)

Top row: Network images under simulated conditions of no enzyme and static 40% strain (A), enzyme and no stretched (B), and enzyme and static 40% strain allowing breaking (C). Color is proportional to force (color bar below B) increasing from blue to red. Note the increased degradation and heterogeneity in structure in (C). Note also that in (B) colors are bluish representing less force due to weakening of springs whereas in (C) colors are similar to those in (A) despite weakening of springs. This is due to load transfer following breaking. (D,F) shows selected time courses of experimentally obtained normalized Young's moduli (Y) and normalized nonlinearity index k. (E,G) shows normalized Y and k from the network model demonstrating a good correspondence with the experimental data.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940411&req=5

Figure 9: Top row: Network images under simulated conditions of no enzyme and static 40% strain (A), enzyme and no stretched (B), and enzyme and static 40% strain allowing breaking (C). Color is proportional to force (color bar below B) increasing from blue to red. Note the increased degradation and heterogeneity in structure in (C). Note also that in (B) colors are bluish representing less force due to weakening of springs whereas in (C) colors are similar to those in (A) despite weakening of springs. This is due to load transfer following breaking. (D,F) shows selected time courses of experimentally obtained normalized Young's moduli (Y) and normalized nonlinearity index k. (E,G) shows normalized Y and k from the network model demonstrating a good correspondence with the experimental data.
Mentions: Figure 9 shows example configurations of the network model before (Figure 9A) and after digestion in the absence (Figure 9B) and presence (Figure 9C) of stretch. The stiffness of the networks was calculated at 15 and 36% strains along the stress-strain curve similarly to the experimental data. The normalized stiffness and nonlinearity index are compared to the corresponding experimental results in Figures 9D–G. It can be seen that the network model matches the trends seen in the experimental data well. The network image in Figure 9C also displays a similar pattern of airspace enlargement seen in the confocal images in Figure 6.

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