Abstract:

Chemotaxis and migration of mammalian cells are important for life processes. Many key physiological processes rely on cell migration, from embryonic development to bone and angiogenesis, playing key roles in tissue repair, inflammation, immune response and cancer metastasis. In vivo, cells must be able to sense various cues in their environment and move toward or away from them in order to execute morphogenetic programs, generate immune responses, and repair damaged tissue during development. When this process goes awry, it can have devastating consequences. Failure of cells to migrate in an appropriate manner can lead to developmental and immune deficiencies, chronic wounds that never heal, and diseases such as aggressive metastatic cancer, autoimmune disease, and fibrosis. The mechanism of cell migration is to transmit chemical and physical cues in the environment to the intracellular signaling network through surface receptors and mechanosensing molecules, establishing asymmetric biochemical gradients in cells, and activating downstream cytoskeletal regulators to polarize cells. The whole process involves various extracellular environmental cues, receptors that transmit cues to the cell, second messengers, and cytoskeleton regulators. The discovery of new chemotactic regulatory molecules and more detailed mechanisms will lead to a more accurate understanding of biomolecular composition and regulatory network organization during cell chemotaxis, which will provide more help for optimal design. Therefore, a systematic understanding of the process of cell chemotaxis is of great significance for developing the rational design and engineering capabilities of synthetic biology in mammalian cells. It will be an important direction of mammalian cell engineering to engineer the chemotaxis and migration ability of cells to achieve artificial control of cell migration, which can help us explore the mechanism of development, improve the effect of immunotherapy, cure diseases caused by cell chemotaxis disorders, and speed up the repair of tissue damage. This review will review and introduce the chemotactic migration of mammalian cells from the aspects of cell chemotactic migration, environmental cues, molecular mechanisms, engineering, and clinical applications.

Key words: cell chemotaxis, environmental clues, migration mode, molecular mechanism, engineering transformation

摘要：

哺乳动物细胞的趋化与迁移对于生命过程重要。许多关键生理过程依赖于细胞迁移，从胚胎发育到骨和血管生成，细胞迁移在组织修复、炎症、免疫应答和癌症转移中起关键作用。在人体内，细胞必须能够感知所在环境中的各种线索，并趋向或远离这些线索，以便在发育过程中执行形态发生程序，面对病原体产生免疫以及修复受损组织。这些过程的失控会给生命带来严重的不良后果，细胞如果不能以适当的方式进行迁移，就会导致发育和免疫的缺陷、慢性伤口的无法愈合以及癌症侵袭性转移、自身免疫和纤维化等疾病。细胞迁移的机制是通过表面受体和机械感知分子将环境中的化学、物理线索传递给细胞内信号网络，通过在细胞内建立不对称的分子空间梯度，激活下游细胞骨架调控因子使细胞发生持续的极化现象。整个过程涉到将线索传递到胞内的膜受体、胞内第二信使、细胞骨架调节因子、肌动蛋白组装等一系列组分和步骤。因此系统性理解细胞趋化过程对于发展哺乳动物细胞合成生物学理性设计与改造能力具有重要意义。工程化改造细胞趋化迁移能力来实现对细胞迁移的人工控制，将是哺乳动物细胞工程的重要方向。这能帮助人们进一步探索发育机制，提升免疫治疗效果，治愈由细胞趋化紊乱造成的疾病，加快组织损伤的修复。本综述将从细胞趋化的迁移方式、环境线索、分子机制、工程改造、临床应用几个方面对哺乳动物细胞的趋化迁移进行综述介绍。

关键词: 细胞趋化, 环境感知, 迁移模式, 分子机制, 工程改造