美国加州大学旧金山分校Wendell A. Lim团队利用合成的细胞粘附分子对多细胞组装进行编程。2022年12月12日，《自然》杂志在线发表了这项研究成果。

研究人员表明，通过将正交的细胞外相互作用与来自原生的粘附分子（如钙粘着蛋白和整合素）的细胞内结构域相结合，可以产生广泛的合成细胞粘附分子（synCAM）。由此产生的分子能够产生定制的细胞-细胞相互作用，其粘附特性类似于原生的相互作用。synCAM的细胞内结构域在指定界面形态和力学方面占主导地位，而不同的同型或异型细胞外相互作用结构域独立地指定细胞之间的连接。这种正交粘附分子的工具箱能够合理地编程组装新的多细胞结构，以及系统地重塑原生的组织。synCAM的模块化提供了关于不同类别的细胞-细胞界面如何演变的基本见解。总之，这些工具为细胞和组织工程以及系统地研究多细胞组织提供了强大的新能力。

据悉，细胞粘附分子在多细胞生物体中无处不在，在组织发育、免疫细胞运输和神经系统连接等不同过程中指定了精确的细胞-细胞相互作用。

附：英文原文

Title: Programming Multicellular Assembly with Synthetic Cell Adhesion Molecules

Author: Stevens, Adam J., Harris, Andrew R., Gerdts, Josiah, Kim, Ki H., Trentesaux, Coralie, Ramirez, Jonathan T., McKeithan, Wesley L., Fattahi, Faranak, Klein, Ophir D., Fletcher, Daniel A., Lim, Wendell A.

Issue&Volume: 2022-12-12

Abstract: Cell adhesion molecules are ubiquitous in multicellular organisms, specifying precise cell-cell interactions in processes as diverse as tissue development, immune cell trafficking, and wiring of the nervous system.1–4 Here, we show that a wide array of synthetic cell adhesion molecules (synCAMs) can be generated by combining orthogonal extracellular interactions with intracellular domains from native adhesion molecules, such as cadherins and integrins. The resulting molecules yield customized cell-cell interactions with adhesion properties similar to native interactions. The synCAM intracellular domain identity dominates in specifying interface morphology and mechanics, while diverse homotypic or heterotypic extracellular interaction domains independently specify the connectivity between cells. This toolkit of orthogonal adhesion molecules enables rationally programmed assembly of novel multicellular architectures, as well as systematic remodeling of native tissues. The modularity of synCAMs provides fundamental insights into how distinct classes of cell-cell interfaces may have evolved. Overall, these tools offer powerful new capabilities for cell and tissue engineering and for systematically studying multicellular organization.

DOI: 10.1038/s41586-022-05622-z

Source: https://www.nature.com/articles/s41586-022-05622-z