StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells.
StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells.
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DOI：
10.1038/s41467-021-26236-5
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发表时间：
2021-10-21
影响因子：
16.6
通讯作者：
Chalut KJ
中科院分区：
文献类型：
--
作者：
Labouesse C;Tan BX;Agley CC;Hofer M;Winkel AK;Stirparo GG;Stuart HT;Verstreken CM;Mulas C;Mansfield W;Bertone P;Franze K;Silva JCR;Chalut KJ
机械信号的研究通常通过比较在软和硬水凝胶基基质上培养的细胞来进行。然而，它是具有挑战性的，独立和稳健地控制基板刚度和细胞外基质拴系基板，使基质拴系的机械信号研究中的一个潜在的混淆变量。此外，不稳定的基质束缚可导致差的细胞附着和细胞粘附的弱接合。为了解决这一问题，我们开发了StemBond水凝胶，这是一种基质栓系牢固且可独立于刚度变化的水凝胶。我们通过证明StemBond水凝胶为培养小鼠和人类多能干细胞提供了最佳系统来验证StemBond水凝胶。我们进一步展示了软StemBond水凝胶如何调节干细胞功能，部分通过刚度敏感的ERK信号传导。我们的研究结果强调了基质力学如何影响调节自我更新和分化的机械敏感信号通路，表明优化完整的机械微环境将对干细胞命运规范提供更大的控制。独立控制基板刚度和拴系的细胞外基质基板的机械信号研究仍然具有挑战性。在这里，作者提出了StemBond水凝胶，具有稳定的ECM栓系，可以独立于刚度而变化，并使用这些来调节小鼠和人类多能干细胞的功能。
Studies of mechanical signalling are typically performed by comparing cells cultured on soft and stiff hydrogel-based substrates. However, it is challenging to independently and robustly control both substrate stiffness and extracellular matrix tethering to substrates, making matrix tethering a potentially confounding variable in mechanical signalling investigations. Moreover, unstable matrix tethering can lead to poor cell attachment and weak engagement of cell adhesions. To address this, we developed StemBond hydrogels, a hydrogel in which matrix tethering is robust and can be varied independently of stiffness. We validate StemBond hydrogels by showing that they provide an optimal system for culturing mouse and human pluripotent stem cells. We further show how soft StemBond hydrogels modulate stem cell function, partly through stiffness-sensitive ERK signalling. Our findings underline how substrate mechanics impact mechanosensitive signalling pathways regulating self-renewal and differentiation, indicating that optimising the complete mechanical microenvironment will offer greater control over stem cell fate specification. The independent control of substrate stiffness and tethering of extracellular matrix to substrates for mechanical signalling investigations remains challenging. Here the authors present StemBond hydrogels, with stable ECM tethering that can be varied independently of stiffness, and use these to modulate the function of mouse and human pluripotent stem cells.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
23.9
作者：
De Belly H;Stubb A;Yanagida A;Labouesse C;Jones PH;Paluch EK;Chalut KJ
通讯作者：
Chalut KJ
影响因子：
9.7
作者：
Ali, Shahzad;Wall, Ivan B.;Veraitch, Farlan S.
通讯作者：
Veraitch, Farlan S.
影响因子：
64.8
作者：
Barriga EH;Franze K;Charras G;Mayor R
通讯作者：
Mayor R
影响因子：
3.7
作者：
Chowdhury F;Li Y;Poh YC;Yokohama-Tamaki T;Wang N;Tanaka TS
通讯作者：
Tanaka TS