Gelator Length Precisely Tunes Supramolecular Hydrogel Stiffness and Neuronal Phenotype in 3D Culture,ACS Biomaterials Science & Engineering

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Gelator Length Precisely Tunes Supramolecular Hydrogel Stiffness and Neuronal Phenotype in 3D Culture
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-01-17 , DOI: 10.1021/acsbiomaterials.9b01585
Jacqueline M Godbe _{1,

2} , Ronit Freeman ₁ , Lena F Burbulla ₃ , Jacob Lewis ₄ , Dimitri Krainc ₃ , Samuel I Stupp _{1,

2,

4,

5}

Affiliation

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 on 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 three-dimensional neuronal cell cultures and transplantation matrices for neural regeneration.

中文翻译：

胶凝剂长度精确调节 3D 培养中的超分子水凝胶硬度和神经元表型

大脑是体内最软的组织之一，其储能模量 ( G ') 根据解剖区域的不同，范围从数百到数千帕斯卡 (Pa)。此外，损伤、衰老和疾病等病理过程可能会导致整个中枢神经系统的机械性能发生微妙的变化。然而，机械性能的这些变化位于极其狭窄的模量范围内，人们对了解它们对神经元生物学的影响非常感兴趣。我们在这里报告了基于阴离子肽两亲物纳米纤维的超分子水凝胶的设计，使用不同分子长度的寡聚-l-赖氨酸来精确调节感兴趣范围内的凝胶刚度，并发现每增加一个赖氨酸单体， G '增加10.5 Pa寡聚-L-赖氨酸链。我们发现，储能模量约 70 Pa 的微小变化会显着影响诱导多能干细胞衍生的多巴胺能神经元的存活、神经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调整水凝胶机械刚度的策略，用于三维神经元细胞培养和神经再生移植基质。

更新日期：2020-01-21

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