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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 modulus at 15% strain normalized to unity at time 0 during 60 min in the tissue bath with or without adding bacterial collagenase. C0% and C40% are control groups without collagenase held, respectively, at 0 or 40% uniaxial strain during the 60 min. D0%, D20%, D40%, and D80% represent groups that were digested with collagenase and held at 0, 20, 40, or 80% strain, respectively. (B) Comparison of the percent decrease in the normalized moduli from time 0 to 60 min. Each bar is statistically significantly different from the other.
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Figure 3: (A) Time course of mean and SD of modulus at 15% strain normalized to unity at time 0 during 60 min in the tissue bath with or without adding bacterial collagenase. C0% and C40% are control groups without collagenase held, respectively, at 0 or 40% uniaxial strain during the 60 min. D0%, D20%, D40%, and D80% represent groups that were digested with collagenase and held at 0, 20, 40, or 80% strain, respectively. (B) Comparison of the percent decrease in the normalized moduli from time 0 to 60 min. Each bar is statistically significantly different from the other.

Mentions: The time evolution of Y was normalized to unity at time t = 0 for various unstretched and static stretched groups including control unstretched (C0%, n = 9), control 40% stretched (C40%, n = 7), control 80% stretched (C80%, n = 6), digested unstretched (D0%, n = 10), digested and stretched at 20% (D20%, n = 7), 40% (D40%, n = 10), and 80% (D80%, n = 7). Generally, the digestion decreased Y in time whereas Y stayed constant (C40%, C80%) or slightly but statistically significantly increased (C0%) in time in the control samples. Since the C80% group was identical to the C40%, it was not included in further analysis. The time courses of Y in the remaining groups are compared in Figure 3A. First, a three-way ANOVA was applied including data from the C0%, C40%, D0%, and D40% groups. This analysis indicated the presence of strong interactions among time, stretch, and digestion. Specifically, we found that (1) the effect of time significantly depended on whether the samples were stretched (40% strain) or not (0% strain; p < 0.001), (2) the effect of time also significantly depended on whether the samples were control (C0% and C40%) or digested (D0% and D40%; p < 0.001), and (3) the effect of digestion significantly depended on whether the samples were at 0 or 40% strain. Next, we compared the percent decrease in Y of all groups at 60 min (Figure 3B) using one-way ANOVA which showed that all groups were statistically significantly different from each other (p < 0.001). It is notable that the drop in Y after 60 min of digestion in the D20% group was significantly smaller than in both the D0% and D40% 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 modulus at 15% strain normalized to unity at time 0 during 60 min in the tissue bath with or without adding bacterial collagenase. C0% and C40% are control groups without collagenase held, respectively, at 0 or 40% uniaxial strain during the 60 min. D0%, D20%, D40%, and D80% represent groups that were digested with collagenase and held at 0, 20, 40, or 80% strain, respectively. (B) Comparison of the percent decrease in the normalized moduli from time 0 to 60 min. Each bar is statistically significantly different from the other.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: (A) Time course of mean and SD of modulus at 15% strain normalized to unity at time 0 during 60 min in the tissue bath with or without adding bacterial collagenase. C0% and C40% are control groups without collagenase held, respectively, at 0 or 40% uniaxial strain during the 60 min. D0%, D20%, D40%, and D80% represent groups that were digested with collagenase and held at 0, 20, 40, or 80% strain, respectively. (B) Comparison of the percent decrease in the normalized moduli from time 0 to 60 min. Each bar is statistically significantly different from the other.
Mentions: The time evolution of Y was normalized to unity at time t = 0 for various unstretched and static stretched groups including control unstretched (C0%, n = 9), control 40% stretched (C40%, n = 7), control 80% stretched (C80%, n = 6), digested unstretched (D0%, n = 10), digested and stretched at 20% (D20%, n = 7), 40% (D40%, n = 10), and 80% (D80%, n = 7). Generally, the digestion decreased Y in time whereas Y stayed constant (C40%, C80%) or slightly but statistically significantly increased (C0%) in time in the control samples. Since the C80% group was identical to the C40%, it was not included in further analysis. The time courses of Y in the remaining groups are compared in Figure 3A. First, a three-way ANOVA was applied including data from the C0%, C40%, D0%, and D40% groups. This analysis indicated the presence of strong interactions among time, stretch, and digestion. Specifically, we found that (1) the effect of time significantly depended on whether the samples were stretched (40% strain) or not (0% strain; p < 0.001), (2) the effect of time also significantly depended on whether the samples were control (C0% and C40%) or digested (D0% and D40%; p < 0.001), and (3) the effect of digestion significantly depended on whether the samples were at 0 or 40% strain. Next, we compared the percent decrease in Y of all groups at 60 min (Figure 3B) using one-way ANOVA which showed that all groups were statistically significantly different from each other (p < 0.001). It is notable that the drop in Y after 60 min of digestion in the D20% group was significantly smaller than in both the D0% and D40% 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