关键词: 化学合成生物学, 受体聚集, 元件工程, 生物医学工程, 细胞调控

Abstract:

Cell surface receptors are important membrane proteins that play a crucial role in mediating signal transduction between the intra- and extracellular environments, which sense extracellular chemical or physical stimuli through their extracellular structures to transmit and amplify signals into the cell through their transmembrane domains, ultimately leading to cellular decision-making. Cell surface receptor clustering is a key molecular mechanism for precisely recognizing extracellular signals and initiating internal signaling cascade responses. The clustering and activation of cell surface receptors are essential for various biological processes such as cell migration, proliferation, apoptosis, and differentiation. In addition, mutations in membrane receptors can lead to the abnormal activation of intracellular signaling pathways, contributing to the pathogenesis of various diseases, such as cancer, diabetes, and atherosclerosis. Given the close relevance of receptor-mediated cellular functions to health and disease, researchers have devoted great effort to exploring the biophysical principles of receptor signal transduction and activation, as well as developing diverse molecular engineering strategies for manipulating receptor activation and the corresponding cellular function. With the emergence and rapid development of chemical synthetic biology, molecular engineering tools have been developed, making the rational regulation of receptor activation much simpler as well as more precise and diverse. This review first summarizes the key functional modules involved in regulating receptor clustering, including molecular recognition, spatial organization, dynamics, and cell-selective modules. We then highlight the latest research advances in highly controllable functional modules enabling the artificial engineering of receptor clusters with dynamic aggregation, specific responsiveness, temporal and spatial resolution, and high cell selectivity. Moreover, we emphasize the emerging applications of various precise molecular strategies for artificially controlling receptor clustering to manipulate cellular phenotypes and cell fates, including immune activation and in vivo tissue regeneration. Finally, we perspective the unresolved issues and challenges in developing receptor clustering strategies, pertaining to the mechanisms of receptor clustering, designs of molecular recognition modules, limitations of clinical applications, safety and long-term in vivo uses, and the potential applications of these strategies in disease treatment.

Key words: chemical synthetic biology, receptor clustering, component engineering, biomedical engineering, cell regulation