Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.
Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.
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DOI：
10.1371/journal.pone.0248256
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Lemmon CA
中科院分区：
文献类型：
--
作者：
Weinberg SH;Saini N;Lemmon CA
细胞外基质蛋白纤连蛋白（FN）组装成不溶性的粘弹性原纤维是胚胎发育和伤口愈合过程中的关键步骤; FN原纤维组装的失调与许多疾病有关，包括纤维化疾病和癌症。我们以前已经开发了一个计算模型的FN原纤维大会，概括的形态和力学的细胞衍生的FN原纤维。在这里，我们使用这个模型来探测两个重要的问题：如何是FN原纤维的形成受细胞的收缩表型，以及如何是FN原纤维的形成受周围组织的刚度？我们表明，FN原纤维的形成强烈依赖于细胞的收缩表型，但只有弱的体外基板刚度，这是一个模拟体内组织刚度。这些结果与以前的实验数据是一致的，并提供了一个更好的洞察条件，促进FN原纤维组装。我们还研究了两种不同的表型FN原纤维，我们以前已经确定，我们表明，这两种表型的比例取决于基板刚度和收缩表型，中间收缩性和高基板刚度创造一个最佳条件，稳定拉伸原纤维。最后，我们研究了纤维的再拉伸如何影响细胞反应。我们探讨了如何收缩表型的再拉伸细胞的影响力学的原纤维;结果表明，肌球蛋白马达的数量只微弱地影响细胞的反应，但增加肌动蛋白速度的结果在减少的表观刚度的原纤维和减少的稳定施加的力的原纤维。两者合计，这些结果提供了新的见解基板刚度和FN原纤维组装细胞收缩性的组合效应。
Assembly of the extracellular matrix protein fibronectin (FN) into insoluble, viscoelastic fibrils is a critical step during embryonic development and wound healing; misregulation of FN fibril assembly has been implicated in many diseases, including fibrotic diseases and cancer. We have previously developed a computational model of FN fibril assembly that recapitulates the morphometry and mechanics of cell-derived FN fibrils. Here we use this model to probe two important questions: how is FN fibril formation affected by the contractile phenotype of the cell, and how is FN fibril formation affected by the stiffness of the surrounding tissue? We show that FN fibril formation depends strongly on the contractile phenotype of the cell, but only weakly on in vitro substrate stiffness, which is an analog for in vivo tissue stiffness. These results are consistent with previous experimental data and provide a better insight into conditions that promote FN fibril assembly. We have also investigated two distinct phenotypes of FN fibrils that we have previously identified; we show that the ratio of the two phenotypes depends on both substrate stiffness and contractile phenotype, with intermediate contractility and high substrate stiffness creating an optimal condition for stably stretched fibrils. Finally, we have investigated how re-stretch of a fibril affects cellular response. We probed how the contractile phenotype of the re-stretching cell affects the mechanics of the fibril; results indicate that the number of myosin motors only weakly affects the cellular response, but increasing actin velocity results in a decrease in the apparent stiffness of the fibril and a decrease in the stably-applied force to the fibril. Taken together, these results give novel insights into the combinatorial effects of substrate stiffness and cell contractility on FN fibril assembly.
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DOI：
10.1039/c5ib00217f
发表时间：
2015-11
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Scott LE;Mair DB;Narang JD;Feleke K;Lemmon CA
通讯作者：
Lemmon CA
DOI：
10.1083/jcb.141.2.539
发表时间：
1998-04-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Zhong C;Chrzanowska-Wodnicka M;Brown J;Shaub A;Belkin AM;Burridge K
通讯作者：
Burridge K
影响因子：
3.4
作者：
Lemmon, Christopher A.;Chen, Christopher S.;Romer, Lewis H.
通讯作者：
Romer, Lewis H.
影响因子：
14
作者：
Salmeron-Sanchez, Manuel;Rico, Patricia;Garcia, Andres J.
通讯作者：
Garcia, Andres J.
DOI：
10.3109/15419069609014219
发表时间：
1996-01-01
期刊：
CELL ADHESION AND COMMUNICATION
影响因子：
--
作者：
Wu, CY;Hughes, PE;McDonald, JA
通讯作者：
McDonald, JA