Gelator length precisely tunes supramolecular hydrogel stiffness and neuronal phenotype in 3D culture.

Gelator length precisely tunes supramolecular hydrogel stiffness and neuronal phenotype in 3D culture.
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DOI:
10.1021/acsbiomaterials.9b01585
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发表时间:
2020-02-10
影响因子:
5.8
通讯作者:
Stupp SI
Stupp SI
中科院分区:
工程技术2区
文献类型:
--
作者:
Godbe JM;Freeman R;Burbulla LF;Lewis J;Krainc D;Stupp SI

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脑是身体中最软的组织之一,其储能模量(G ')取决于解剖区域而在数百至数千帕斯卡(Pa)的范围内。此外,损伤、衰老和疾病等病理过程会导致整个中枢神经系统的机械性能发生微妙变化。然而,这些机械性能的变化是在一个非常狭窄的范围内的模量和有很大的兴趣,了解它们对神经元生物学的影响。我们在这里报告的设计的超分子水凝胶的阴离子肽两亲物纳米纤维的基础上,使用不同的分子长度的寡-L-赖氨酸,以精确地调整凝胶刚度在感兴趣的范围内,并发现G'增加了10.5帕的每个额外的赖氨酸单体的寡-L-赖氨酸链。我们发现储能模量在70 Pa量级的微小变化显著影响来自诱导多能干细胞的多巴胺能神经元的存活、轴突生长和酪氨酸羟化酶阳性群体。这里报道的工作提供了一种策略,以调整用于3D神经元细胞培养和神经再生移植基质的水凝胶的机械刚度。
The brain is one of the softest tissues in the body with storage moduli (G’) that range from hundreds to thousands of pascals (Pa) depending upon the anatomic region. Furthermore, pathological processes such as injury, aging and disease can cause subtle changes in the mechanical properties throughout the central nervous system. However, these changes in mechanical properties lie within an extremely narrow range of moduli and there is great interest in understanding their effect on neuron biology. We report here the design of supramolecular hydrogels based on anionic peptide amphiphile nanofibers using oligo-L-lysines of different molecular lengths to precisely tune gel stiffness over the range of interest and found that G’ increases by 10.5 Pa for each additional lysine monomer in the oligo-L-lysine chain. We found that small changes in storage modulus on the order of 70 Pa significantly affect survival, neurite growth and tyrosine hydroxylase-positive population in dopaminergic neurons derived from induced pluripotent stem cells. The work reported here offers a strategy to tune mechanical stiffness of hydrogels for use in 3D neuronal cell cultures and transplantation matrices for neural regeneration.
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