Mechanical strain stabilizes reconstituted collagen fibrils against enzymatic degradation by mammalian collagenase matrix metalloproteinase 8 (MMP-8).
Mechanical strain stabilizes reconstituted collagen fibrils against enzymatic degradation by mammalian collagenase matrix metalloproteinase 8 (MMP-8).
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DOI：
10.1371/journal.pone.0012337
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发表时间：
2010-08-23
期刊：
影响因子：
3.7
通讯作者：
Ruberti JW
中科院分区：
文献类型：
--
作者：
Flynn BP;Bhole AP;Saeidi N;Liles M;Dimarzio CA;Ruberti JW
胶原蛋白是一种三螺旋自组织蛋白，是哺乳动物的主要结构蛋白。它存在于骨、韧带、肌腱、软骨、椎间盘、皮肤、血管和角膜中。我们最近假设，纤维状胶原蛋白（及其互补酶）包括一个智能结构系统的基础上，似乎支持分子的保留在原纤维的拉伸机械应变。该理论表明，驱动胶原蛋白在负载组织中优先积累的机制在分子水平上起作用，而不仅仅是细胞驱动的。这一概念将基质形态的控制减少到分子与最相关的、物理的和持久的信号：机械应变之间的相互作用。研究在环境控制的微生物反应器中进行，其中在微量移液管之间轻轻地拉紧重构的I型胶原微网。应变的微网暴露于活性基质金属蛋白酶8（MMP-8）和加载和卸载的原纤维的相对降解速率，同时使用无标记差分干涉对比（DIC）成像跟踪。结果发现，施加的拉伸机械应变显着增加的降解时间加载的原纤维相比，卸载，配对的控制。在许多情况下，在未应变的原纤维降解很久之后，应变的原纤维是可检测的。在这项调查中，我们证明了第一次施加的机械应变优先保留胶原纤维的存在下，一种生理上重要的哺乳动物酶：MMP-8。这些结果有可能有助于我们了解许多胶原基质现象，包括发育、适应、重塑和疾病。此外，组织工程可以受益于从生理上相容的和可变的胶原蛋白雕刻所需结构的能力。
Collagen, a triple-helical, self-organizing protein, is the predominant structural protein in mammals. It is found in bone, ligament, tendon, cartilage, intervertebral disc, skin, blood vessel, and cornea. We have recently postulated that fibrillar collagens (and their complementary enzymes) comprise the basis of a smart structural system which appears to support the retention of molecules in fibrils which are under tensile mechanical strain. The theory suggests that the mechanisms which drive the preferential accumulation of collagen in loaded tissue operate at the molecular level and are not solely cell-driven. The concept reduces control of matrix morphology to an interaction between molecules and the most relevant, physical, and persistent signal: mechanical strain. The investigation was carried out in an environmentally-controlled microbioreactor in which reconstituted type I collagen micronetworks were gently strained between micropipettes. The strained micronetworks were exposed to active matrix metalloproteinase 8 (MMP-8) and relative degradation rates for loaded and unloaded fibrils were tracked simultaneously using label-free differential interference contrast (DIC) imaging. It was found that applied tensile mechanical strain significantly increased degradation time of loaded fibrils compared to unloaded, paired controls. In many cases, strained fibrils were detectable long after unstrained fibrils were degraded. In this investigation we demonstrate for the first time that applied mechanical strain preferentially preserves collagen fibrils in the presence of a physiologically-important mammalian enzyme: MMP-8. These results have the potential to contribute to our understanding of many collagen matrix phenomena including development, adaptation, remodeling and disease. Additionally, tissue engineering could benefit from the ability to sculpt desired structures from physiologically compatible and mutable collagen.
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影响因子：
2.9
作者：
COMPER, WD;VEIS, A
通讯作者：
VEIS, A
DOI：
10.1073/pnas.48.6.1014
发表时间：
1962-01-01
影响因子：
11.1
作者：
GROSS, J;LAPIERE, CM
通讯作者：
LAPIERE, CM
DOI：
10.1115/1.1406131
发表时间：
2001-12-01
影响因子：
1.7
作者：
Humphrey, JD
通讯作者：
Humphrey, JD
影响因子：
3.8
作者：
COWIN, SC
通讯作者：
COWIN, SC
影响因子：
3.9
作者：
Basser, PJ;Schneiderman, R;Maroudas, A
通讯作者：
Maroudas, A