Logic-Based Delivery of Site-Specifically Modified Proteins from Environmentally Responsive Hydrogel Biomaterials.
Logic-Based Delivery of Site-Specifically Modified Proteins from Environmentally Responsive Hydrogel Biomaterials.
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DOI：
10.1002/adma.201902462
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发表时间：
2019-08
期刊：
影响因子：
--
通讯作者：
DeForest CA
中科院分区：
文献类型：
--
作者：
Gawade PM;Shadish JA;Badeau BA;DeForest CA
材料中蛋白质的受控表达对许多生物工程应用仍然具有重要意义。虽然“智能”平台可以控制响应单一外部提示的蛋白质释放，但目前还没有开发出一种策略来触发响应用户指定的环境输入组合的释放，也没有开发出一种策略来独立控制同质材料中多个物种的释放。在这项工作中，我们引入了一种模块化的半合成方案，以控制根据布尔逻辑从水凝胶中释放位点特异性修饰的蛋白质。利用排序酶介导的转肽化反应生成c端通过环境敏感的可降解连接物连接到凝胶上的重组蛋白。通过改变这些可定制的连接物中多个刺激不稳定部分的连通性，我们详尽地证明了在涉及酶、还原剂和光的单输入和双输入组合下蛋白质释放的YES/OR/AND控制。通过不同的刺激敏感连接器将多种蛋白质捆绑在一起，使它们能够独立地、顺序地从共同的材料中释放出来。我们期望这些方法能够在组织工程和治疗递送方面带来新的机会。根据环境输入的精确组合，水凝胶生物材料中特定位点修饰蛋白的程序化释放使用布尔是/或/与逻辑指定。通过将蛋白质固定在凝胶上的可降解部分的明确安装，可以从普通材料中获得顺序和独立控制的蛋白质释放。
The controlled presentation of proteins from and within materials remains of significant interest for many bioengineering applications. Though “smart” platforms offer control over protein release in response to a single external cue, no strategy has been developed to trigger delivery in response to user-specified combinations of environmental inputs, nor to independently control the release of multiple species from a homogenous material. In this work, we introduce a modular semisynthetic scheme to govern the release of site-specifically modified proteins from hydrogels following Boolean logic. A sortase-mediated transpeptidation reaction was used to generate recombinant proteins C-terminally tethered to gels through environmentally sensitive degradable linkers. By varying the connectivity of multiple stimuli-labile moieties within these customizable linkers, we exhaustively demonstrate YES/OR/AND control of protein release in response to one and two-input combinations involving enzyme, reductant, and light. Tethering of multiple proteins each through a different stimuli-sensitive linker permits their independent and sequential release from a common material. We expect these methodologies to enable new opportunities in tissue engineering and therapeutic delivery. The programmed release of site-specifically modified proteins from hydrogel biomaterials in response to precise combinations of environmental inputs is specified using Boolean YES/OR/AND logic. Sequential and independently controlled release of proteins from a common material is afforded through well-defined installation of degradable moieties tethering the protein to the gel.
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