Fine-Tuning the Degree of Stem Cell Polarization and Alignment on Ordered Arrays of High-Aspect-Ratio Nanopillars
Fine-Tuning the Degree of Stem Cell Polarization and Alignment on Ordered Arrays of High-Aspect-Ratio Nanopillars
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DOI：
10.1021/nn301654e
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发表时间：
2012-07-01
期刊：
影响因子：
17.1
通讯作者：
Aizenberg, Joanna
中科院分区：
文献类型：
--
作者：
Bucaro, Michael A.;Vasquez, Yolanda;Aizenberg, Joanna
纳米生物材料正在引入新的能力来协调细胞选择，生长，形态和分化。在这里，我们报告说，调整纳米柱（NP）的有序阵列的几何形状eliminates粘附细胞的专门形态。NP半径，高度和间距的影响的系统分析表明，干细胞假设扁平，极化，或星状形态直接响应柱间间距。值得注意的是，在间距接近临界间距（对于C3 H10 T1/2细胞，d（crit）近似于2 μ m）的NP上，细胞表现出细胞体的变圆、明显的极化和与NP阵列的正方形晶格对齐并延伸数百微米的窄轴突样细胞突起的延伸。此外，将NP的纵横比从12：1增加到50：1以产生NP弯曲刚度相应降低2个数量级的NP，放大了细胞响应，并导致先前未见过的细胞极化和排列程度。快速形态转化在保持NP几何形状和间距的关键参数的表面上是可再现的，受细胞接种密度的影响，并且对于不同的干细胞系和原代间充质干细胞持续存在。通过简单地调整NP底物的几何形状来支持干细胞中的各种形态发生趋势的能力为未来设计细胞形态和对齐至关重要的支架提供了垫脚石。
Nanobiomaterials are introducing new capabilities to coordinate cell selection, growth, morphology, and differentiation. Herein, we report that tuning the geometry of ordered arrays of nanopillars (NP) elicits specialized morphologies in adherent cells. Systematic analysis of the effects of the NP radius, height, and spacing reveals that stem cells assume either flattened, polarized, or stellate morphologies in direct response to interpillar spacing. Notably, on NPs of pitch near a critical spacing (d(crit) approximate to 2 mu m for C3H10T1/2 cells), cells exhibit rounding of the cell body, pronounced polarization, and extension of narrow axon-like cell projections aligned with the square lattice of the NP array and extending hundreds of micrometers. Furthermore, increasing the NPs' aspect ratio from 12:1 to 50:1 to produce NPs with a corresponding reduction in the NP bending stiffness of 2 orders of magnitude amplified the cellular response and resulted in a previously unseen degree of cell polarization and alignment. The rapid morphological transformation is reproducible on surfaces that maintain key parameters of the NP geometry and spacing, is influenced by the cell seeding density, and persists for different stem cell lines and primary mesenchymal stem cells. The demonstrated ability to support various morphogenetic trends in stem cells by simply tuning the geometry of the NP substrates provides a stepping-stone for the future design of scaffolds where cellular morphology and alignment are crucial.