Department of Genetics, Harvard Medical School, Boston, MA, USA.
Wyss Institute, Harvard Medical School, Boston, MA, USA.
Trends Cell Biol. 2024 Apr;34(4):277-287. doi: 10.1016/j.tcb.2023.07.007. Epub 2023 Aug 12.
Intercellular interactions form the cornerstone of multicellular biology. Despite advances in protein engineering, researchers artificially directing physical cell interactions still rely on endogenous cell adhesion molecules (CAMs) alongside off-target interactions and unintended signaling. Recently, methods for directing cellular interactions have been developed utilizing programmable domains such as coiled coils (CCs), nanobody-antigen, and single-stranded DNA (ssDNA). We first discuss desirable molecular- and systems-level properties in engineered CAMs, using the helixCAM platform as a benchmark. Next, we propose applications for engineered CAMs in immunology, developmental biology, tissue engineering, and neuroscience. Biologists in various fields can readily adapt current engineered CAMs to establish control over cell interactions, and their utilization in basic and translational research will incentivize further expansion in engineered CAM capabilities.
细胞间相互作用是多细胞生物学的基石。尽管在蛋白质工程方面取得了进展，但研究人员在人为指导物理细胞相互作用时仍然依赖于内源性细胞粘附分子 (CAMs) 以及脱靶相互作用和意外信号转导。最近，已经开发出了利用可编程结构域（如卷曲螺旋 (CC)、纳米体-抗原和单链 DNA (ssDNA)）来指导细胞相互作用的方法。我们首先使用 helixCAM 平台作为基准，讨论了工程化 CAMs 在分子和系统水平上的理想特性。接下来，我们提出了工程化 CAM 在免疫学、发育生物学、组织工程和神经科学中的应用。各个领域的生物学家可以轻松地采用当前的工程化 CAM 来控制细胞间的相互作用，并且它们在基础研究和转化研究中的应用将激励工程化 CAM 能力的进一步扩展。
