A genetically encoded adhesin toolbox for programming multicellular morphologies and patterns
A genetically encoded adhesin toolbox for programming multicellular morphologies and patterns
复制标题
用于编程多细胞形态和模式的基因编码粘附素工具箱
DOI：
10.1101/240721
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ingmar H. Riedel
中科院分区：
文献类型：
--
作者：
David S. Glass;Ingmar H. Riedel
合成多细胞系统有望了解生物膜和高等生物的自然发育1,2，以及设计复杂的多组分代谢途径2,3 和材料4。然而，此类努力需要工具将细胞粘附到定义的形态和模式中，而这些工具目前缺乏1,5,6。在这里，我们报告了第一个用于大肠杆菌模块化细胞间粘附的 100% 基因编码合成平台，它提供了对多细胞自组装的控制。粘附选择性由外膜展示的纳米抗体 7,8 和具有正交库内特异性的抗原肽文库提供，而亲和力则由内在粘附素亲和力、竞争性抑制和诱导表达控制。我们展示了通过同质和异质相互作用、晶格状自组装、相分离、差异粘附和顺序分层合理设计明确的形态和图案的能力。该粘附工具箱与合成生物学标准兼容9，将能够构建高水平的多细胞设计，并揭示向多细胞性的进化过渡6,10。
Synthetic multicellular systems hold promise for understanding natural development of biofilms and higher organisms1,2, as well as for engineering complex multi-component metabolic pathways2,3 and materials4. However, such efforts will require tools to adhere cells into defined morphologies and patterns, and these tools are currently lacking1,5,6. Here we report the first 100% genetically encoded synthetic platform for modular cell-cell adhesion in Escherichia coli, which provides control over multicellular self-assembly. Adhesive selectivity is provided by a library of outer membrane-displayed nanobody7,8 and antigen peptides with orthogonal intra-library specificities, while affinity is controlled by intrinsic adhesin affinity, competitive inhibition, and inducible expression. We demonstrate the resulting capabilities for rational design of well-defined morphologies and patterns through homophilic and heterophilic interactions, lattice-like self-assembly, phase separation, differential adhesion, and sequential layering. This adhesion toolbox, compatible with synthetic biology standards9, will enable construction of high-level multicellular designs and shed light on the evolutionary transition to multicellularity6,10.
DOI：
10.1002/smll.201502972
发表时间：
2015-12-22
期刊：
Small (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Koo H;Choi M;Kim E;Hahn SK;Weissleder R;Yun SH
通讯作者：
Yun SH
影响因子：
5.4
作者：
Lyons NA;Kolter R
通讯作者：
Kolter R