Sprouting angiogenesis induces significant mechanical heterogeneities and ECM stiffening across length scales in fibrin hydrogels.
Sprouting angiogenesis induces significant mechanical heterogeneities and ECM stiffening across length scales in fibrin hydrogels.
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DOI：
10.1016/j.biomaterials.2018.02.012
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发表时间：
2018-04
期刊：
影响因子：
14
通讯作者：
Putnam AJ
中科院分区：
文献类型：
--
作者：
Juliar BA;Keating MT;Kong YP;Botvinick EL;Putnam AJ
基质刚度是二维细胞培养中公认的指导性线索。由于缺乏合适的方法来量化与单个细胞-细胞外基质 (ECM) 相互作用相关的长度尺度上的刚度，其在 3 维 (3D) 培养物形态发生中的作用以及细胞对其周围微环境力学的反向影响更加难以捉摸。在本研究中，我们应用传统的体流变学和基于激光镊子的主动微流变学来探测 3D 毛细血管形态发生的复杂多细胞过程中跨长度尺度的力学，并进一步表征了新生血管和支持性基质细胞对刚度随时间动态变化的相对贡献。我们的数据显示，萌芽毛细血管周围的局部 ECM 硬度高度不均匀，并且这种变化随着时间的推移逐渐增加。内皮细胞和基质支持细胞都逐渐使 ECM 变硬，其中后者主导了体积特性的变化。有趣的是，如共焦反射显微镜所示，具有高微观刚度的区域并不一定与高 ECM 密度的重塑区域相关。总的来说，这些发现，特别是软 3D 纤维蛋白凝胶形态发生过程中细胞周围局部刚度的巨大时空变化，强调了跨长度尺度的 ECM 力学特征提供了一个机会，可以从机械生物学上更深入地了解微环境在细胞命运和组织模式中的作用。
Matrix stiffness is a well-established instructive cue in two-dimensional cell cultures. Its roles in morphogenesis in 3-dimensional (3D) cultures, and the converse effects of cells on the mechanics of their surrounding microenvironment, have been more elusive given the absence of suitable methods to quantify stiffness on a length-scale relevant for individual cell-extracellular matrix (ECM) interactions. In this study, we applied traditional bulk rheology and laser tweezers-based active microrheology to probe mechanics across length scales during the complex multicellular process of capillary morphogenesis in 3D, and further characterized the relative contributions of neovessels and supportive stromal cells to dynamic changes in stiffness over time. Our data show local ECM stiffness was highly heterogeneous around sprouting capillaries, and the variation progressively increased with time. Both endothelial cells and stromal support cells progressively stiffened the ECM, with the changes in bulk properties dominated by the latter. Interestingly, regions with high micro-stiffness did not necessarily correlate with remodeled regions of high ECM density as shown by confocal reflectance microscopy. Collectively, these findings, especially the large spatiotemporal variations in local stiffness around cells during morphogenesis in soft 3D fibrin gels, underscore that characterizing ECM mechanics across length scales provides an opportunity to attain a deeper mechanobiological understanding of the microenvironment’s roles in cell fate and tissue patterning.
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影响因子：
3.7
作者：
Kotlarchyk MA;Shreim SG;Alvarez-Elizondo MB;Estrada LC;Singh R;Valdevit L;Kniazeva E;Gratton E;Putnam AJ;Botvinick EL
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作者：
Lee, P. -F.;Bai, Y.;Smith, R. L.;Bayless, K. J.;Yeh, A. T.
通讯作者：
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细胞介导的纤维募集驱动工程原纤维微环境中的细胞外基质机械感应。
影响因子：
41.2
作者：
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通讯作者：
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