Self-Assembly of Structured Colloidal Gels for High-Resolution 3D Micropatterning of Proteins at Scale
Self-Assembly of Structured Colloidal Gels for High-Resolution 3D Micropatterning of Proteins at Scale
复制标题
用于大规模蛋白质高分辨率 3D 微图案化的结构化胶体凝胶自组装
DOI：
10.1002/adma.202304461
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发表时间：
2023
影响因子：
29.4
通讯作者：
Ramnarine-Sanchez R
中科院分区：
文献类型：
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作者：
Ramnarine-Sanchez R
自组装，即将部件自发地排序成模式，在本质上是普遍的，也是跨长度尺度产生功能的基础。生物发育中的形态梯度既是自组装的产物，也是自组装的效应器，人们已经进行了各种尝试，以在生物材料设计中重现这种梯度。到目前为止，这些方法通常使用自上而下的制造技术，虽然允许高分辨率控制，但受到规模的限制，需要化学交联步骤来及时稳定形态图案。在这里，一种自下而上的蛋白质构型方法是基于一种新的二元反应-扩散过程，其中蛋白质作为扩散反应物组装成纳米粘土-蛋白质复合水凝胶。使用这种方法，仅通过粘土纳米颗粒与血液中存在的蛋白质和离子之间的物理相互作用，就可以生成可扩展和高度稳定的目标蛋白质的3D图案，分辨率达到亚细胞分辨率。图案化的纳米粘土凝胶能够引导细胞行为，精确地模板骨组织在体内的形成。这些结果证明了通过自组装过程稳定生物信号的3D梯度的可行性，并为基于形态原的治疗策略和生物发育和修复的模型开辟了新的可能性。
Self‐assembly, the spontaneous ordering of components into patterns, is widespread in nature and fundamental to generating function across length scales. Morphogen gradients in biological development are paradigmatic as both products and effectors of self‐assembly and various attempts have been made to reproduce such gradients in biomaterial design. To date, approaches have typically utilized top‐down fabrication techniques that, while allowing high‐resolution control, are limited by scale and require chemical cross‐linking steps to stabilize morphogen patterns in time. Here, a bottom‐up approach to protein patterning is developed based on a novel binary reaction‐diffusion process where proteins function as diffusive reactants to assemble a nanoclay‐protein composite hydrogel. Using this approach, it is possible to generate scalable and highly stable 3D patterns of target proteins down to sub‐cellular resolution through only physical interactions between clay nanoparticles and the proteins and ions present in blood. Patterned nanoclay gels are able to guide cell behavior to precisely template bone tissue formation in vivo. These results demonstrate the feasibility of stabilizing 3D gradients of biological signals through self‐assembly processes and open up new possibilities for morphogen‐based therapeutic strategies and models of biological development and repair.