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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

(A) Time course of mean and SD of the normalized modulus during 60 min with or without adding bacterial collagenase. The amplitudes and frequencies of sinusoidal stretching around the static strain of 40% are given in parentheses. For comparison, the 40% static stretch data without error bars (D40%) is also shown by dashed gray line. (B) Comparison of the percent change in the normalized moduli from time 0 to 60 min. The static D40% (0%0) from Figure 3B is different from all dynamic cases and the D10%–0.1 Hz case different from the D20%–1 Hz case. (C) The nonlinearity index for which there was a significant increase with time but there was no difference among the groups.
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Figure 5: (A) Time course of mean and SD of the normalized modulus during 60 min with or without adding bacterial collagenase. The amplitudes and frequencies of sinusoidal stretching around the static strain of 40% are given in parentheses. For comparison, the 40% static stretch data without error bars (D40%) is also shown by dashed gray line. (B) Comparison of the percent change in the normalized moduli from time 0 to 60 min. The static D40% (0%0) from Figure 3B is different from all dynamic cases and the D10%–0.1 Hz case different from the D20%–1 Hz case. (C) The nonlinearity index for which there was a significant increase with time but there was no difference among the groups.

Mentions: Figure 5A compares the time courses of the dynamically stretched and digested groups denoted by 10%, 0.1 (n = 5), 10%, 1 (n = 5), 20%, 0.1 (n = 5), and 20%, 1 (n = 8) where the first number is the dynamic strain amplitude around the 40% static strain and the second number is the frequency in Hz. Interestingly, all of the dynamic groups showed significantly stronger decrease with time than the static D40% group. Three-way ANOVA demonstrates a significant effect of time (p < 0.001) and interactions between frequency and amplitude of stretching around a static mean stretch of 40% (p < 0.01). While the effect of time did not depend on what level of frequency or amplitude was present, the effect of frequency (0.1 or 1 Hz) on Y significantly depended on what level of amplitude (10 or 20%) was present (p < 0.01). Specifically, a larger decrease was observed (1) at 1 Hz than at 0.1 Hz at 20% dynamic strain amplitude and (2) at 20% amplitude than at 10% amplitude but only at 1 Hz. The percent decreases in Y at 60 min are compared with each other and the static case of D40% (from Figure 3B) in Figure 5B. The static D40% is different from all dynamic cases (p < 0.001) and the 10%, 0.1 Hz case is different from the 20%, 1 Hz case suggesting that the higher frequency and larger amplitude cyclic stretching enhances enzymatic degradation of lung tissue. Figure 5C shows the time course of the normalized nonlinearity index for which there was a significant increase with time (p < 0.001) but there was no difference among the groups.


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)

(A) Time course of mean and SD of the normalized modulus during 60 min with or without adding bacterial collagenase. The amplitudes and frequencies of sinusoidal stretching around the static strain of 40% are given in parentheses. For comparison, the 40% static stretch data without error bars (D40%) is also shown by dashed gray line. (B) Comparison of the percent change in the normalized moduli from time 0 to 60 min. The static D40% (0%0) from Figure 3B is different from all dynamic cases and the D10%–0.1 Hz case different from the D20%–1 Hz case. (C) The nonlinearity index for which there was a significant increase with time but there was no difference among the groups.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 5: (A) Time course of mean and SD of the normalized modulus during 60 min with or without adding bacterial collagenase. The amplitudes and frequencies of sinusoidal stretching around the static strain of 40% are given in parentheses. For comparison, the 40% static stretch data without error bars (D40%) is also shown by dashed gray line. (B) Comparison of the percent change in the normalized moduli from time 0 to 60 min. The static D40% (0%0) from Figure 3B is different from all dynamic cases and the D10%–0.1 Hz case different from the D20%–1 Hz case. (C) The nonlinearity index for which there was a significant increase with time but there was no difference among the groups.
Mentions: Figure 5A compares the time courses of the dynamically stretched and digested groups denoted by 10%, 0.1 (n = 5), 10%, 1 (n = 5), 20%, 0.1 (n = 5), and 20%, 1 (n = 8) where the first number is the dynamic strain amplitude around the 40% static strain and the second number is the frequency in Hz. Interestingly, all of the dynamic groups showed significantly stronger decrease with time than the static D40% group. Three-way ANOVA demonstrates a significant effect of time (p < 0.001) and interactions between frequency and amplitude of stretching around a static mean stretch of 40% (p < 0.01). While the effect of time did not depend on what level of frequency or amplitude was present, the effect of frequency (0.1 or 1 Hz) on Y significantly depended on what level of amplitude (10 or 20%) was present (p < 0.01). Specifically, a larger decrease was observed (1) at 1 Hz than at 0.1 Hz at 20% dynamic strain amplitude and (2) at 20% amplitude than at 10% amplitude but only at 1 Hz. The percent decreases in Y at 60 min are compared with each other and the static case of D40% (from Figure 3B) in Figure 5B. The static D40% is different from all dynamic cases (p < 0.001) and the 10%, 0.1 Hz case is different from the 20%, 1 Hz case suggesting that the higher frequency and larger amplitude cyclic stretching enhances enzymatic degradation of lung tissue. Figure 5C shows the time course of the normalized nonlinearity index for which there was a significant increase with time (p < 0.001) but there was no difference among the groups.

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