Development Of Nucleic Acid Nanomaterials Towards Cell Function Mimicking

Nucleic acid,as a carrier of genetic information,widely exists in the life system.At the same time,nucleic acid is used to construct various nanostructures w ith different functions based on the principle of Watson-Crick base pairing.As a stable,programmable and designaable structure,nucleic acid structure is widely used in the construction of molecular machines and biomimicking system.Based on the unique advantages of self-assembling DNA structure and DNA nanostructure,we combined DNA structure with cell extrated vesicle,which was cell mimicking model,to simulate the structure and function of cell systems.We designed and constructed biomimicking systems which equipped with cell adaptive behavior and signal transmission between artificial cells.The major contents are as follows:(1)In chapter 2,we synthesized a lipid-modified nucleic acid sequence using the DNA solid-phase synthesizer.The DNA sequence has amphiphilic properties similar to phospholipid monomer,which self-assemble into DNA micelle structure in queous solution.The DNA sequence of DNA micelle initiated hybridization chain reaction and regulated the size of DNA micelle.Moreover,we found the DNA micelle structure has abundant attachment sites for drug.With the help of aptamer whch modified on the surface of DNA micelle structure,the DNA structure delivered drug into target cells and killed target cells.(2)In chapter 3,we selected the vesicle which extracted from cells and was more similar to nature cell for reseach.To anchore DNA structures on membrane of vesicle,we modified cholesterol to DNA structures.We explored the toehold mediated strand displacement reaction dyn amics between three different DNA structures(double-strand DNA structure,DNA triangular prism,DNA trtrahedron)with single-strand DNA structure on the mebrane of vesicle.We obtained the reaction rules of different DNA structures on membrane,which lay the foundation for subsequent research.(3)In chapter 4,based on DNA strand displacement reaction and hybridization chain reaction,we constructed a DNA-based artificial signal system on the membrane of vesicle to mimicking cell adaptivity.To accomplish thi s mechanistically,our equipped specific DNA sequences on the membrane of vesicle which not only can sense incoming stimuli but also can emit a feedback response to eliminate the stimuli.Moreover,our biomimicking system achieved recyclicable responses to stimulus.Our reseach provide a new thought for the construction of artificial cells that can respond to complex environmental stimuli.(4)In chapter 5,we constructed two kinds of artificial cell by modified different DNA structure on the vesicle.The toehol d-mediated strand displacement reaction was initiated by the conract of different artificial cells,and the products can open the DNA-based nanopore which inserted into membrane,then realized the activation of signal conduction between different artificia l cells.Our research provides a basis for the construction of the more intelligent artificial cell in the future.