Transmembrane Signal Transduction Based On DNA Biomimetic Membrane Receptor

Transmembrane signal transduction refers to the biological process that external signals triger the conformation change of the membrane protein receptor on cell membrane,and transmit new signals into the membrane to regulate the biological functionalities in cells.Biomimetic construction of transmembrane signaling systems have potential applications in chemical biosensing,drug-controlled delivery,and cellular signaling.DNA could be served as biomimetic materials due to its advantages of sequence controllable hybridization,convenient program design,stimuli-response,and good biocompatibility.Based on the excellent properties of DNA nucleic acid aptamers and G-quadruplex,two biomimetic membrane receptors with biomolecular and photo-controlled responses were designed and used for transmembrane signal transduction.The specific researches are as follows:1.Based on adenosine-mediated transmembrane G-quadruplex formation and enzymatic signal amplification,biomimetic dimerization membrane receptors were designed.An adenosine aptamer was used as a recognition element,a split G-quaduplex was used as a signal output element,and a carbon-12 spacer was used as a bridging molecule to construct a pair of dimer biomimetic tr ansmembrane receptors.The addition of extracellular adenosine molecules induces the dimerization of biomimetic membrane receptors on the membrane,and the formation of G-quadruplex and,which in turn triggers the ABTS colorimetric reaction and Amplex red fluorescence generation in the vesicles.Thus signal transmembrane conduction can be established.The formation of dimers of biomimetic membrane receptors was characterized by electrophoresis,circular dichroism,fluorescence reson ance energy transfer and total internal reflection fluorescence microscopy.The membrane signal transduction experiments of vesicles showed that the rate of ABTS colorimetric reaction and the Amplex red fluorescence reaction were increased to 2.5-fold in the presence of 1 mM adenosine.This work proposes a DNA-based dimer biomimetic membrane receptor and provides a new biomimetic model for transmembrane signal transduction.2.Based on UV-visible light modulated-transmembrane G-quadruplex formation and enzymatic signal amplification,biomimetic dimerization membrane receptors were designed.A pair of dimer biomimetic transmembrane receptors were constructed using azobenzene as a light-controlled response element and a split G-quadruplex as a signal output element.Azobenzene was demonstrated cis-trans configuration change reversibly under UV-Vis irradiation.UV irradiation prompts the azobenzene in a cis structure,that inhibits the hybrization of DNA and G-quadruplex formation due to steric hindrance.However,visible irradiation prompts the azobenzene in a trans structure,that allows the hybrization of DNA and G-quadruplex formation.This process subsequently triggers the ABTS colorimetric reaction and Amplex red fluorescence generation in the vesicle,thereby achieving transmembrane enzymatic reaction activation and signal transduction.The photo-controlled dimer formation of biomimetic membrane receptors was characterized by electrophoresis,circular dichroism,fluorescence resonance energy transfer and total inte rnal reflection fluorescence microscopy.The membrane signal transduction experiments of vesicles showed that compared with ultraviolet light,visible light irradiation promoted a 4.0-fold and a 1.5-fold rate increase in the ABTS colorimetric reaction and the Amplex red fluorescence reaction,respectively.This work proposed a light-stimuli dimeric biomimetic membrane receptor and this component could be used in biosensing,drug controlled delivery,etc.