Flow-Induced Crystallization of Collagen: A Potentially Critical Mechanism in Early Tissue Formation.

Flow-Induced Crystallization of Collagen: A Potentially Critical Mechanism in Early Tissue Formation.
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DOI:
10.1021/acsnano.5b07756
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发表时间:
2016-05-24
期刊:
影响因子:
17.1
通讯作者:
Ruberti JW
Ruberti JW
中科院分区:
材料科学1区
文献类型:
--
作者:
Paten JA;Siadat SM;Susilo ME;Ismail EN;Stoner JL;Rothstein JP;Ruberti JW

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I型胶原蛋白单体是自然界最精致和最普遍的结构工具之一。它的300纳米三螺旋基序组装成坚韧的细胞外纤维,无缝地跨越组织边界过渡,并超过细胞尺寸高达4个数量级。尽管进行了广泛的研究,但没有现有的模型令人满意地解释了这种连续结构是如何在需要的地方(在力的路径中对齐)通过离散的微尺度细胞使用纳米尺度的材料精确地生成和生长的。我们提出了一个简单的纤维拉伸实验,它表明,稍微浓缩的I型胶原单体可以“流动结晶”,形成高度定向,连续,分层纤维在细胞可实现的应变速率(<1 s−1)和生理相关的浓度(100 μM)。我们还表明,拉伸过程后施加张力保持了纤维的结构完整性。虽然机械张力已被证明是在发育中的动物的组织形态发生期间驱动胶原原纤维形成的关键因素,但力在构建组织的过程中的确切作用尚不清楚。我们的数据直接耦合机械张力,特别是拉伸应变率,胶原纤维组装。我们进一步推导出一个“生长方程”,该方程预测,无论是全球性的肌肉发育或局部成纤维细胞的拉伸应变的应用,可以迅速驱动已经形成的短原纤维的融合,以产生长距离的,连续的纤维。结果提供了一种可扩展的结缔组织制造的途径,并支持体内胶原纤维沉积和生长的机械生物学模型。
The type I collagen monomer is one of nature's most exquisite and prevalent structural tools. Its 300 nm triple-helical motifs assemble into tough extracellular fibers that transition seamlessly across tissue boundaries and exceed cell dimensions by up to 4 orders of magnitude. In spite of extensive investigation, no existing model satisfactorily explains how such continuous structures are generated and grown precisely where they are needed (aligned in the path of force) by discrete, microscale cells using materials with nanoscale dimensions. We present a simple fiber drawing experiment, which demonstrates that slightly concentrated type I collagen monomers can be “flow-crystallized” to form highly oriented, continuous, hierarchical fibers at cell-achievable strain rates (<1 s−1) and physiologically relevant concentrations (∼50 μM). We also show that application of tension following the drawing process maintains the structural integrity of the fibers. While mechanical tension has been shown to be a critical factor driving collagen fibril formation during tissue morphogenesis in developing animals, the precise role of force in the process of building tissue is not well understood. Our data directly couple mechanical tension, specifically the extensional strain rate, to collagen fibril assembly. We further derive a “growth equation” which predicts that application of extensional strains, either globally by developing muscles or locally by fibroblasts, can rapidly drive the fusion of already formed short fibrils to produce long-range, continuous fibers. The results provide a pathway to scalable connective tissue manufacturing and support a mechano-biological model of collagen fibril deposition and growth in vivo.
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发表时间: 1993-08-01
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影响因子: 14
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