Tuning Viscoelasticity in Alginate Hydrogels for 3D Cell Culture Studies.
Tuning Viscoelasticity in Alginate Hydrogels for 3D Cell Culture Studies.
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DOI：
10.1002/cpz1.124
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Chaudhuri O
中科院分区：
文献类型：
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作者：
Charbonier F;Indana D;Chaudhuri O
细胞外基质（ECM）的物理性质影响细胞行为，从细胞粘附和迁移到分化和基因表达;这一过程称为机械转导。虽然大多数研究都集中在ECM刚度的影响，使用线性弹性材料，如聚丙烯酰胺凝胶作为细胞培养基质，生物组织和ECM是粘弹性的，这意味着它们表现出时间依赖性的机械响应和耗散机械能。最近的研究表明，ECM粘弹性，独立的刚度，作为一个关键的物理参数调节细胞过程。这些研究使用具有可调粘弹性的生物材料作为细胞培养基质，其中藻酸盐水凝胶是最常用的系统之一。在这里，我们详细介绍了三种方法来调节粘弹性藻酸盐水凝胶的二维和三维细胞培养研究的协议，以及其机械性能的测试。藻酸盐水凝胶中的粘弹性可以通过改变藻酸盐聚合物的分子量、改变交联剂的类型-离子型与共价型、或通过将短聚（乙二醇）（PEG）链接枝到藻酸盐聚合物来调节。由于这些方法是基于商业上可获得的产品和简单的化学反应，这些协议应该是在细胞生物学和生物工程界的科学家访问。
Physical properties of the extracellular matrix (ECM) affect cell behaviors ranging from cell adhesion and migration to differentiation and gene expression; a process known as mechanotransduction. While most studies have focused on the impact of ECM stiffness, using linearly elastic materials such as polyacrylamide gels as cell culture substrates, biological tissues and ECMs are viscoelastic, which means they exhibit time-dependent mechanical responses and dissipate mechanical energy. Recent studies have revealed ECM viscoelasticity, independent of stiffness, as a critical physical parameter regulating cellular processes. These studies have used biomaterials with tunable viscoelasticity as cell-culture substrates, with alginate hydrogels being one of the most commonly used systems. Here, we detail the protocols for three approaches to modulating viscoelasticity in alginate hydrogels for 2D and 3D cell culture studies, as well as the testing of their mechanical properties. Viscoelasticity in alginate hydrogels can be tuned by varying the molecular weight of the alginate polymer, changing the type of crosslinker – ionic vs covalent, or by grafting short poly(ethylene-glycol) (PEG) chains to the alginate polymer. As these approaches are based on commercially available products and simple chemistries, these protocols should be accessible for scientists in the cell biology and bioengineering communities.