Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis.
Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis.
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具有可调机械可塑性的水凝胶调节血管发生和血管生成中的内皮细胞生长。
DOI：
10.1038/s41467-023-43768-0
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发表时间：
2023-12-14
影响因子：
16.6
通讯作者：
Xu, Feng
中科院分区：
文献类型：
--
作者：
Wei, Zhao;Lei, Meng;Wang, Yaohui;Xie, Yizhou;Xie, Xueyong;Lan, Dongwei;Jia, Yuanbo;Liu, Jingyi;Ma, Yufei;Cheng, Bo;Gerecht, Sharon;Xu, Feng
内皮细胞（endothelial cell，EC）在血管发生和血管生成中的生长都始于周围基质的重塑，并随着细胞间的相互作用而进行，以形成多细胞血管。基质的机械可塑性，定义为通过外部牵引永久变形的能力，在调节细胞行为中是关键的。然而，基质可塑性对EC生长过程中细胞间相互作用的影响，沿着相关的分子途径，仍然难以捉摸。在这里，我们开发了一个胶原-透明质酸为基础的水凝胶平台，通过使用动态和共价网络的合成策略，具有可调的可塑性。我们发现，虽然增加的水凝胶的可塑性有利于基质重塑的EC，最大的管腔和最长的侵入距离出乎意料地出现在水凝胶与介质的可塑性，而不是最高的。我们揭示了水凝胶的高可塑性促进了EC的稳定整合素簇和粘着斑激酶的募集，其具有显著增强的收缩性，其下调血管内皮钙粘蛋白表达并使单个EC之间的粘附连接不稳定。我们的研究结果，进一步验证了数学模拟和体内血管生成试验，表明基质可塑性的平衡有利于细胞-基质结合和细胞-细胞粘附，促进血管组装和侵袭。揭示细胞外基质对内皮细胞（EC）生长的影响对于理想地控制血管形成至关重要，但基质可塑性对EC生长的作用是难以捉摸的。在这里，作者开发了具有独立于刚度的可调机械可塑性的水凝胶，并阐明了血管发生和血管生成过程中EC的可塑性介导的反应。
The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as the ability to permanently deform by external traction, is pivotal in modulating cell behaviors. Nevertheless, the implications of matrix plasticity on cell-to-cell interactions during EC outgrowth, along with the molecular pathways involved, remain elusive. Here we develop a collagen-hyaluronic acid based hydrogel platform with tunable plasticity by using compositing strategy of dynamic and covalent networks. We show that although the increasing plasticity of the hydrogel facilitates the matrix remodeling by ECs, the largest tubular lumens and the longest invading distance unexpectedly appear in hydrogels with medium plasticity instead of the highest ones. We unravel that the high plasticity of the hydrogels promotes stable integrin cluster of ECs and recruitment of focal adhesion kinase with an overenhanced contractility which downregulates the vascular endothelial cadherin expression and destabilizes the adherens junctions between individual ECs. Our results, further validated with mathematical simulations and in vivo angiogenic tests, demonstrate that a balance of matrix plasticity facilitates both cell-matrix binding and cell-to-cell adherens, for promoting vascular assembly and invasion. It is vital to unveil the effects of extracellular matrix cues on endothelial cell (EC) outgrowth for desirably governing vasculature formation, but the role of matrix plasticity on EC outgrowth is elusive. Here, the authors develop hydrogels with tunable mechanical plasticity independent of stiffness, and elucidate the plasticity-mediated responses of ECs during vasculogenesis and angiogenesis.
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胶原蛋白的机械可塑性指导人类乳腺类器官的分支伸长。
影响因子：
16.6
作者：
Buchmann B;Engelbrecht LK;Fernandez P;Hutterer FP;Raich MK;Scheel CH;Bausch AR
通讯作者：
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影响因子：
4
作者：
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通讯作者：
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DOI：
10.1073/pnas.2008801117
发表时间：
2020-10-20
影响因子：
11.1
作者：
Grolman, Joshua M.;Weinand, Philipp;Mooney, David J.
通讯作者：
Mooney, David J.
影响因子：
6
作者：
Bayless, KJ;Salazar, R;Davis, GE
通讯作者：
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影响因子：
3.8
作者：
Ding，Yilei;Zhao，An-sha;Yang，Ping
通讯作者：
Yang，Ping