| The development of life science has enabled humans to have a deeper understanding of the biomolecules that make up life.The well-known four major types of biomolecules include nucleic acids,proteins,carbohydrates and phospholipids.And most of biomolecules have advanced nanostructures,exhibiting physicochemical properties that are distinct from macroscopic objects.In recent decades,progresses in nanotechnology have enabled humans to directly manipulate biomolecules at the molecular level.Through rational design,these biomolecules can be assembled and constructed into specific functional structures,molecular manipulation tools,and nanodevices.In this field,DNA nanotechnology has recently attracted lots of intersts in the world.Generally speaking,DNA is the genetic information carrier of natural life and plays a vital role in genetic information storage and transmission.In addition,various topological nanostructures can be designed and constructed by using the strong coding property and addressability of DNA materials.At present,it has been widely used in the cross-research fields of chemistry,materials,biology and medicine.Biomembrane that includes cell membrane,is an indispensable interface and medium for life science research.It is not only the boundary of cells but also directly participates in the whole life process,which has a significant impact on cells and even individual life.In this paper,we selected cell and a giant biomimetic vesicle that developed by our research team as the research object,and investigated the interaction of DNA nanostructure in biomembrane.Finally,we realized the molecular dynamic manipulation in the biomembrane system.The research work is of great significance for constructing chemical biosensors on biomembarne surface,realizing a series of simple and rapid biosensing strategies and clinical disease diagnosis,providing a powerful technology for biomedicine to overcome biological barrier and improve drug delivery efficiency.These works is expected to be widely used in the field of interface intelligent molecular machines,artificial cell construction and molecular clinical diagnosis.Based on these issues,this thesis 1)is devoted to the self-assembly of DNA molecules into nanostructures for biomimetic and material research,and 2)to design dynamic molecular manipulation based on DNA molecules for cancer cell surface recognition and artificial cell study.The details are as follows:In Chapter 2,cholesterol-modified DNA strands have been used extensively as molecular anchoring tools for biomembrane.In this chapter,we discovered and reported that under acidic conditions,cholesterol-modified DNA strands can self-assemble into spherical micelles and one-dimensional nanorods.Studies have shown that nanorods are assembled by multiple layers of micelles,and the morphology of the nanorods can be adjusted by changing the assembly environment and the sequence of DNA.The self-assembly behavior of cholesterol-modified DNA nanostructures under acidic conditions can provide a new design strategy for designing self-assemblies based on amphiphilic DNA block copolymers in the future.In Chapter 3,based on a giant biomimetic vesicle developed by our laboratory,we used DNA nanoprism as a three-dimensional structure model to realize the reversible regulation of DNA nanoprism on the surface of the biomimetic vesicle.The assembly and disassembly of DNA nanoprisms on the surface of biomimetic vesicles were achieved by DNA strand hybridization and strand displacement reactions.The issue of assembly and regulation of DNA nanostructures on the surface of living cell becomes very difficult due to the endocytosis of cells to nanomaterials and the highly dynamic properties of cell membranes.Since the vesicle is derived from the cell and processing a micron-sized chamber,it provides a powerful research platform for the interaction between DNA nanostructures and biological interfaces.In Chapter 4,we reported on a small three-dimensional DNA logic machine for cell surface-specific dual recognition and logic calculations.It uses the simplest DNA three-dimensional nanoprism as the structural skeleton,and then installs two molecular recognition toes and an operational toe on the skeleton.The machine will only start on a specific cell surface.Through the integrated "AND" logic gate calculation to generate a specific response signal,the specific recognition of the cell surface is achieved,which greatly improves the accuracy of recognition and shows the potential for accurate diagnosis and treatment of cancer cells.In Chapter 5,we designed and built an artificial molecular signaling system based on giant biomimetic vesicles that mimics the signaling pathways of cells: from external signal reception on the membrane surface,to a series of internal signal transduction,and finally to feedback response.The specific process is under the stimulation of ATP,the DNA nanogatekeeper on the giant biomimetic vesicle membrane switches from the closed state to the open state.This activates the molecular signal network encapsulated in the biomimetic capsular vesicles,which consists of a number of different molecular signal modules,and the final signal feedback module switches the DNA nanogatekeeper back to the closed state.This work rationally integrates static DNA nanostructures and dynamic cascade networks into a single vesicle,demonstrating that DNA-based artificial molecular signaling systems can process external environmental information and simulate complex signaling pathways in cells. |
PDF Full Text Request