Spatially-Encoding Hydrogels With DNA to Control Cell Signaling,Advanced Materials

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Spatially-Encoding Hydrogels With DNA to Control Cell Signaling
Advanced Materials ( IF 27.4 ) Pub Date : 2023-05-23 , DOI: 10.1002/adma.202301086
Namrata Ramani _{1,

2} , C Adrian Figg _{2,

3} , Alex J Anderson _{2,

3} , Peter H Winegar _{2,

3} , EunBi Oh _{2,

3} , Sasha B Ebrahimi _{2,

4} , Devleena Samanta _{2,

3} , Chad A Mirkin _{1,

2,

3}

Affiliation

Patterning biomolecules in synthetic hydrogels offers routes to visualize and learn how spatially-encoded cues modulate cell behavior (e.g., proliferation, differentiation, migration, and apoptosis). However, investigating the role of multiple, spatially defined biochemical cues within a single hydrogel matrix remains challenging because of the limited number of orthogonal bioconjugation reactions available for patterning. Herein, a method to pattern multiple oligonucleotide sequences in hydrogels using thiol-yne photochemistry is introduced. Rapid hydrogel photopatterning of hydrogels with micron resolution DNA features (≈1.5 µm) and control over DNA density are achieved over centimeter-scale areas using mask-free digital photolithography. Sequence-specific DNA interactions are then used to reversibly tether biomolecules to patterned regions, demonstrating chemical control over individual patterned domains. Last, localized cell signaling is shown using patterned protein–DNA conjugates to selectively activate cells on patterned areas. Overall, this work introduces a synthetic method to achieve multiplexed micron resolution patterns of biomolecules onto hydrogel scaffolds, providing a platform to study complex spatially-encoded cellular signaling environments.

中文翻译：

利用 DNA 进行空间编码水凝胶来控制细胞信号传导

合成水凝胶中的生物分子图案化提供了可视化和了解空间编码线索如何调节细胞行为（例如增殖、分化、迁移和凋亡）的途径。然而，由于可用于图案化的正交生物共轭反应的数量有限，研究单个水凝胶基质内多个空间定义的生化线索的作用仍然具有挑战性。本文介绍了一种利用硫醇-炔光化学在水凝胶中对多个寡核苷酸序列进行图案化的方法。使用无掩模数字光刻技术，可以在厘米级区域内实现具有微米分辨率 DNA 特征（约 1.5 µm）的水凝胶快速水凝胶光图案化和对 DNA 密度的控制。然后使用序列特异性 DNA 相互作用将生物分子可逆地束缚到图案区域，从而证明对单个图案结构域的化学控制。最后，使用图案化蛋白质-DNA 缀合物选择性激活图案区域上的细胞来显示局部细胞信号传导。总体而言，这项工作介绍了一种合成方法，可在水凝胶支架上实现生物分子的多重微米分辨率模式，为研究复杂的空间编码细胞信号传导环境提供了一个平台。

更新日期：2023-05-23

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