Limits...
Quantitative evaluation of collagen crosslinks and corresponding tensile mechanical properties in mouse cervical tissue during normal pregnancy.

Yoshida K, Jiang H, Kim M, Vink J, Cremers S, Paik D, Wapner R, Mahendroo M, Myers K - PLoS ONE (2014)

Bottom Line: The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery.Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS).All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Columbia University, New York, New York, United States of America.

ABSTRACT
The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery. Cervical collagens are known to remodel extensively in mice with progressing gestation leading to a soft cervix at term. During this process, mature crosslinked collagens are hypothesized to be replaced with immature less crosslinked collagens to facilitate cervical softening and ripening. To determine the mechanical role of collagen crosslinks during normal mouse cervical remodeling, tensile load-to-break tests were conducted for the following time points: nonpregnant (NP), gestation day (d) 6, 12, 15, 18 and 24 hr postpartum (PP) of the 19-day gestation period. Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). There were no significant changes in the total immature crosslink density (HLNL+DHLNL mol per collagen mol) throughout normal mouse gestation (range: 0.31-0.49). Total mature crosslink density (PYD+DPD mol per collagen mol) decreased significantly in early softening from d6 to d15 (d6: 0.17, d12: 0.097, d15: 0.026) and did not decrease with further gestation. The maturity ratio (total mature to total immature crosslinks) significantly decreased in early softening from d6 to d15 (d6: 0.2, d15: 0.074). All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL. This data provides quantitative evidence to support the hypothesis that as mature crosslinked collagens decline, they are replaced by immature collagens to facilitate increased tissue compliance in the early softening period from d6 to d15.

Show MeSH

Related in: MedlinePlus

DHLNL immature crosslink density correlates with mechanical properties, but not HLNL.Scatter plots showing correlation between immature crosslink densities and mechanical properties. HLNL density on the horizontal axis versus: A) initial stiffness, B) final stiffness, and C) ultimate stress. DHLNL density on the horizontal axis versus: D) initial stiffness, E) final stiffness, and F) ultimate stress. Colors represent gestation groups: NP - blue, d6 - green, d12 - cyan, d15 - magenta, d18 - black, and PP - red. Red line represents simple linear regression line between crosslink density and each mechanical property. Dotted lines represent 95% confidence interval. The -values for regression listed for each correlation with number of *'s representing significance.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4232411&req=5

pone-0112391-g005: DHLNL immature crosslink density correlates with mechanical properties, but not HLNL.Scatter plots showing correlation between immature crosslink densities and mechanical properties. HLNL density on the horizontal axis versus: A) initial stiffness, B) final stiffness, and C) ultimate stress. DHLNL density on the horizontal axis versus: D) initial stiffness, E) final stiffness, and F) ultimate stress. Colors represent gestation groups: NP - blue, d6 - green, d12 - cyan, d15 - magenta, d18 - black, and PP - red. Red line represents simple linear regression line between crosslink density and each mechanical property. Dotted lines represent 95% confidence interval. The -values for regression listed for each correlation with number of *'s representing significance.

Mentions: Collagen crosslink densities (DHLNL, DPD, PYD) and maturity ratio correlated significantly with tissue tensile mechanical properties. We fit a simple linear regression model to the data with the crosslink density as the explanatory variable. For immature crosslinks, there was no significant correlation between HLNL crosslink density with initial and final stiffness (Fig. 5A,B). HLNL crosslink density was negatively correlated to ultimate strength (Fig. 5C). DHLNL crosslink density was significantly and positively correlated to final stiffness and ultimate strength (Fig. 5E,F, ). For mature crosslinks, both DPD and PYD density showed significant positive correlations with final stiffness and ultimate strength with . PYD showed more significant correlations to both mechanical properties in comparison with DPD (Fig. 6B,C,E,F). Despite the lack of correlation between HLNL and mechanical properties, the maturity ratio showed significant correlation with mechanical properties (Fig. 7). The correlation between maturity ratio and final stiffness is summarized and presented a function of progressing gestation in Fig. 8.


Quantitative evaluation of collagen crosslinks and corresponding tensile mechanical properties in mouse cervical tissue during normal pregnancy.

Yoshida K, Jiang H, Kim M, Vink J, Cremers S, Paik D, Wapner R, Mahendroo M, Myers K - PLoS ONE (2014)

DHLNL immature crosslink density correlates with mechanical properties, but not HLNL.Scatter plots showing correlation between immature crosslink densities and mechanical properties. HLNL density on the horizontal axis versus: A) initial stiffness, B) final stiffness, and C) ultimate stress. DHLNL density on the horizontal axis versus: D) initial stiffness, E) final stiffness, and F) ultimate stress. Colors represent gestation groups: NP - blue, d6 - green, d12 - cyan, d15 - magenta, d18 - black, and PP - red. Red line represents simple linear regression line between crosslink density and each mechanical property. Dotted lines represent 95% confidence interval. The -values for regression listed for each correlation with number of *'s representing significance.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232411&req=5

pone-0112391-g005: DHLNL immature crosslink density correlates with mechanical properties, but not HLNL.Scatter plots showing correlation between immature crosslink densities and mechanical properties. HLNL density on the horizontal axis versus: A) initial stiffness, B) final stiffness, and C) ultimate stress. DHLNL density on the horizontal axis versus: D) initial stiffness, E) final stiffness, and F) ultimate stress. Colors represent gestation groups: NP - blue, d6 - green, d12 - cyan, d15 - magenta, d18 - black, and PP - red. Red line represents simple linear regression line between crosslink density and each mechanical property. Dotted lines represent 95% confidence interval. The -values for regression listed for each correlation with number of *'s representing significance.
Mentions: Collagen crosslink densities (DHLNL, DPD, PYD) and maturity ratio correlated significantly with tissue tensile mechanical properties. We fit a simple linear regression model to the data with the crosslink density as the explanatory variable. For immature crosslinks, there was no significant correlation between HLNL crosslink density with initial and final stiffness (Fig. 5A,B). HLNL crosslink density was negatively correlated to ultimate strength (Fig. 5C). DHLNL crosslink density was significantly and positively correlated to final stiffness and ultimate strength (Fig. 5E,F, ). For mature crosslinks, both DPD and PYD density showed significant positive correlations with final stiffness and ultimate strength with . PYD showed more significant correlations to both mechanical properties in comparison with DPD (Fig. 6B,C,E,F). Despite the lack of correlation between HLNL and mechanical properties, the maturity ratio showed significant correlation with mechanical properties (Fig. 7). The correlation between maturity ratio and final stiffness is summarized and presented a function of progressing gestation in Fig. 8.

Bottom Line: The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery.Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS).All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Columbia University, New York, New York, United States of America.

ABSTRACT
The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery. Cervical collagens are known to remodel extensively in mice with progressing gestation leading to a soft cervix at term. During this process, mature crosslinked collagens are hypothesized to be replaced with immature less crosslinked collagens to facilitate cervical softening and ripening. To determine the mechanical role of collagen crosslinks during normal mouse cervical remodeling, tensile load-to-break tests were conducted for the following time points: nonpregnant (NP), gestation day (d) 6, 12, 15, 18 and 24 hr postpartum (PP) of the 19-day gestation period. Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). There were no significant changes in the total immature crosslink density (HLNL+DHLNL mol per collagen mol) throughout normal mouse gestation (range: 0.31-0.49). Total mature crosslink density (PYD+DPD mol per collagen mol) decreased significantly in early softening from d6 to d15 (d6: 0.17, d12: 0.097, d15: 0.026) and did not decrease with further gestation. The maturity ratio (total mature to total immature crosslinks) significantly decreased in early softening from d6 to d15 (d6: 0.2, d15: 0.074). All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL. This data provides quantitative evidence to support the hypothesis that as mature crosslinked collagens decline, they are replaced by immature collagens to facilitate increased tissue compliance in the early softening period from d6 to d15.

Show MeSH
Related in: MedlinePlus