| Cell signaling networks regulate a variety of essential physiological processes,including development,homeostasis,and tissue repair.When the external environment changes,the ligand mediates activation of the cell membrane surface receptors,and then responds to this change by intracellular transduction and amplification of signals to effect specific cellular behaviors（e.g.secretion,movement,growth,division and death）.In order to precisely regulate cell behaviors through specific cell signaling pathways,optical activation has become a powerful tool for controlling cellular functions with high temporal and spatial resolution.Optogenetic tools have been developed to regulate cellular behaviors,enabling precise spatial and temporal control of cellular signals for different cellular behaviors by introducing photoresponsive receptors into cells.However,most of the light control systems have the following drawbacks:a)the require of genetical engineering on the receptor,b)cell damages caused by the widely used ultraviolet light,and c)lack of deep tissue penetration.The above disadvantages limit the in vivo application of optogenetics,such as tissue repair.In this paper,we constructed a near-infrared light-activated DNA agonist（NIR-DA）nanodevice to successfully achieve precise regulation of cell signaling,phenotype and behavior in deep tissues of living organisms.The above NIR-DA nanodevice is assembled from a nucleic acid aptamer-based DNA agonist and gold nanorods（AuNRs）.Under the action of near-infrared light,the local surface of AuNRs undergoes plasmon resonance（LSPR）photothermal effect,releasing and activating DNA agonists.Activated DNA agonists digest the DNA-modified chimeric or native receptor tyrosine kinase（RTK）on the cell surface and activate downstream cell signaling,thereby altering the cellular phenotype and controlling cell behavior.Finally,the study used the NIR-DA system to achieve optical activation of the RTK signal transduction pathway in mice,triggering the migration,proliferation and differentiation of satellite cells in skeletal muscle tissue and promoting skeletal muscle regeneration.The details are as follows:1.Nano-devices that activate DNA agonist by near-infrared light are used to regulate the behavior of chimeric receptor cells.In this chapter,we designed a pair of aptamer-based DNA-protein chimeric receptors by non-genetic engineering.Upon NIR light irradiation,functionalized AuNRs release and activate the DNA agonist,which triggers binding-induced dimerization of RTK,subsequent activation of downstream signal transduction and enhancement of cell behavior.Our experiments demonstrated that near-infrared light illuminates AuNRs@DA to release and activate DNA agonists.Activated DNA agonists dimerize DNA-modified chimeric receptor tyrosine kinase（RTK）on the cell surface and activate downstream cell signaling,thereby altering cell phenotype,controlling cell remodeling,and cell behaviors such as polarization and directional migration.2.Nano-devices that activate DNA agonist by near-infrared light are used to regulate the behavior of natural receptor cells.In order to directly regulate receptors on target cells in complex tissues,we have constructed a NIR-DA system that directly regulates native MET receptors.Our experiments demonstrated that near-infrared light illuminates AuNRs@DAMET to release and activate DAMET agonist.Activated DAMETET agonist directly modulate the natural receptor tyrosine kinase（RTK）dimerization on the cell surface and activate downstream cell signaling,controlling the behavior of cell-directed migration in deep tissues.3.Near-infrared light activated DNA agonist nanodevice for tissue repair.In the previous chapter,we demonstrated that the constructed NIR-activated DAMETET nanodevice can regulate cell behavior in deep tissues.In this chapter we used the NIR-DA system to regulate MET signaling and animal cell behavior.Here,we have demonstrated that the NIR-DA system achieves optical activation of the RTK signal transduction pathway in mice,triggers migration,proliferation and differentiation of satellite cells in skeletal muscle tissue,and promotes skeletal muscle regeneration.The NIR-DA system provides a powerful and versatile platform for exogenous regulation of deep tissue for purposes such as regenerative medicine. |
