Engineering of Nucleic Acids and Synthetic Cofactors as Holo Sensors for Probing Signaling Molecules in the Cellular Membrane Microenvironment

Abstract

The comprehensive understanding of the mechanisms underlying the interaction of cells with their membrane microenvironment is of great value for fundamental biological research; however,tracking biomolecules on cell surfaces with high temporal and spatial resolution remains ac hallenge. Herein, amodular strategy is presented for the construction of cell surface DNA-based sensors by engineering DNAm otifs and synthetic cofactors.I nt his strategy,astimuli-reactive organic molecule is employed as the cofactor for the DNA motif,and the self-assembly of them forms aFRET-based holo DNA-based sensor.Withthe use of the DNA-based sensors,the versatility of this modular strategy has been demonstrated in the ratiometric imaging of the cellular extrusion process of endogenous signaling molecules,i ncluding sulfur dioxide derivatives and nitric oxide.

A Smart, Autocatalytic, DNAzyme Biocircuit for in Vivo, Amplified, MicroRNA Imaging

“…[10a] HCR has ah igh amplification capacity while maintaining al ow background for sensing purpose. [10d] DNAzymes are catalytic nucleic acids [14] that have been recognized as versatile means of signal amplification for the detection of nucleic acids and aptamer-substrate complexes, [15] because of the ease of integrating functional sequences into DNAzymes,t he ease of synthesis and modification, and their intrinsic thermal and chemical resistance.N evertheless,t he effectiveness of these DNAzyme-amplified sensing platforms is constrained by their inherent low catalytic efficiency [16] and the inadequate cofactor supply under cellular environment. [17] Forpromoting the signal amplification of DNAzymes,e fforts have been devoted to its efficient integration with other nonenzymatic amplification approaches,including HCR or CHA systems.…”

A quantitative assessment of the dynamic modification of lipid–DNA probes on live cell membranes

“…4,[6][7][8] Lipid-DNA conjugates can be further modied with different functional moieties, including uorophores, small molecule drugs, chemically reactive crosslinkers, photo-responsive groups, etc. These modications have allowed the engineering of functional lipid-DNA probes to monitor cell membrane transportation of signalling molecules, 12,13 to analyze membrane biophysics, 14,15 to generate membrane nanopores, 16,17 and to regulate intercellular interactions. 18,19 In addition to their broad range of applications on plasma membrane surfaces, lipid-DNA probes can also be used for intracellular applications such as transmembrane cargo deliveries 13,[20][21][22] and membrane analysis of intracellular organelles.…”

A DNAzyme-amplified DNA circuit for highly accurate microRNA detection and intracellular imaging

“…8 They can mimic the functions of protein enzymes and catalyze a wide range of chemical reactions, including DNA ligation and cleavage. [9][10][11] The multiple turnover rate of a DNAzyme turns it into an ideal signal amplication candidate for high-performance biosensing applications. The efficiency of DNAzyme amplication could be improved by integrating its functional sequence with other amplication means.…”