Substrate Modulus Directs Neural Stem Cell Behavior
Substrate Modulus Directs Neural Stem Cell Behavior
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DOI：
10.1529/biophysj.108.132217
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Healy, Kevin E.
中科院分区：
文献类型：
--
作者：
Saha, Krishanu;Keung, Albert J.;Healy, Kevin E.
虽然调节干细胞自我更新和分化的生化信号被广泛研究，但直到最近才显示干细胞微环境的机械特性来调节其行为。这将是可取的，有独立的控制生化和机械的线索，以分析其相对和综合影响干细胞功能。我们开发了一种合成的界面水凝胶培养系统，称为可变模量互穿聚合物网络（vmIPNs），以评估可溶性信号，粘附配体呈递和材料模量从10- 10，000 Pa对成体神经干细胞（aNSC）行为的影响。当在无血清生长培养基中在模量>= 100 Pa的肽修饰的vmIPN上培养时，aNSC增殖。在无血清神经元分化培养基中，在500 Pa的vmIPN上观察到神经元标记物β-微管蛋白III的峰值水平，接近脑组织的生理硬度。此外，在与血清的混合分化条件下，较软的凝胶（类似于100-500 Pa）大大有利于神经元，而较硬的凝胶（类似于1,000 - 10,000 Pa）促进神经胶质细胞培养。与此相反，细胞的扩展，自我更新，和分化的抑制与类似的10 Pa的模量的基质。这项工作表明，可以调节aNSC微环境的机械和生化特性，以调节aNSC的自我更新和分化。
Although biochemical signals that modulate stem cell self-renewal and differentiation were extensively studied, only recently were the mechanical properties of a stem cell's microenvironment shown to regulate its behavior. It would be desirable to have independent control over biochemical and mechanical cues, to analyze their relative and combined effects on stem-cell function. We developed a synthetic, interfacial hydrogel culture system, termed variable moduli interpenetrating polymer networks (vmIPNs), to assess the effects of soluble signals, adhesion ligand presentation, and material moduli from 10-10,000 Pa on adult neural stem-cell (aNSC) behavior. The aNSCs proliferated when cultured in serum-free growth media on peptide-modified vmIPNs with moduli of >= 100 Pa. In serum-free neuronal differentiation media, a peak level of the neuronal marker, beta-tubulin III, was observed on vmIPNs of 500 Pa, near the physiological stiffness of brain tissue. Furthermore, under mixed differentiation conditions with serum, softer gels (similar to 100-500 Pa) greatly favored neurons, whereas harder gels (similar to 1,000 10,000 Pa) promoted glial cultures. In contrast, cell spreading, self-renewal, and differentiation were inhibited on substrata with moduli of similar to 10 Pa. This work demonstrates that the mechanical and biochemical properties of an aNSC microenvironment can be tuned to regulate the self-renewal and differentiation of aNSCs.