Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation
Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation
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DOI：
10.1002/adma.202105460
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发表时间：
2021-11-14
影响因子：
29.4
通讯作者：
Kang, Heemin
中科院分区：
文献类型：
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作者：
Hong, Hyunsik;Min, Sunhong;Kang, Heemin
在天然微环境中，存在多种物理屏障以动态调节干细胞募集和分化用于组织修复。在这项研究中，利用各种尺寸的基于纳米组装的磁性屏幕，它们被弹性地拴在RGD配体（细胞粘附基序）呈递材料表面上，以在屏幕和RGD之间产生各种纳米间隙，而不调节RGD密度。显示低RGD分布的大屏幕刺激整联蛋白聚集以促进干细胞的粘着斑、机械转导和分化，这在小屏幕中未观察到。大屏幕的磁性向下拉动减小了纳米间隙，这动态地抑制了干细胞的粘着斑、机械转导和分化。相反，磁性向上拉动小屏幕会增加纳米间隙，这会动态激活粘着斑、机械转导和干细胞分化。这种调节机制在体内微环境中也被证明是有效的。进一步使物理筛网的几何形状多样化可以进一步实现分布式RGD的多方面和安全的非筛选的多种形式，以解开和调节用于组织修复的干细胞分化。
In native microenvironment, diverse physical barriers exist to dynamically modulate stem cell recruitment and differentiation for tissue repair. In this study, nanoassembly-based magnetic screens of various sizes are utilized, and they are elastically tethered over an RGD ligand (cell-adhesive motif)-presenting material surface to generate various nanogaps between the screens and the RGDs without modulating the RGD density. Large screens exhibiting low RGD distribution stimulate integrin clustering to facilitate focal adhesion, mechanotransduction, and differentiation of stem cells, which are not observed with small screens. Magnetic downward pulling of the large screens decreases the nanogaps, which dynamically suppress the focal adhesion, mechanotransduction, and differentiation of stem cells. Conversely, magnetic upward pulling of the small screens increases the nanogaps, which dynamically activates focal adhesion, mechanotransduction, and differentiation of stem cells. This regulation mechanism is also shown to be effective in the microenvironment in vivo. Further diversifying the geometries of the physical screens can further enable diverse modalities of multifaceted and safe unscreening of the distributed RGDs to unravel and modulate stem cell differentiation for tissue repair.