자료유형  

 학위논문

Control Number  

0016934298

International Standard Book Number  

9798380594912

Dewey Decimal Classification Number  

621

Main Entry-Personal Name  

Wang, Weitao.

Publication, Distribution, etc. (Imprint  

[S.l.] : Carnegie Mellon University., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(159 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-04, Section: B.

General Note  

Advisor: Taylor, Rebecca E.;Ren, Xi.

Dissertation Note  

Thesis (Ph.D.)--Carnegie Mellon University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Recent advances in structural DNA nanotechnology have opened up new avenues for manipulating cellular systems at nanoscale level. The cell plasma membrane, a critical interface governing cellular communication and material transport between cells and their surroundings, presents a promising target for such interventions. Probing, investigating and thus engineering cell membranes will greatly add our understanding on the important role of membranes to cells and unlock exciting prospects for cell-based therapies.The thesis begins by providing an overview of the fundamental structure and function of the cell membrane, highlighting its importance in cellular physiology and function. It then delves into the principles and techniques of structural DNA nanotechnology, covering synthesis, functional modification, purification and characterization, showcasing its unique ability to design and construct user-defined nanostructures with high programmability and specificity. To apply DNA nanostructures to cell membranes, it is critical to understand the way they interact with each other. Building upon the fundamental concepts, I then present approaches developed both within our groups and in the literature to overcome the physical and chemical barriers of cell membranes, and deliver DNA nanostructures to targeted positions on cells. To gain an in-depth insight into the interactions between DNA nanostructures and cell membranes, we apply the state-of-art microscopy technologies, including scanning conductance microscopy and confocal laser scanning microscopy, to provide the first direct observation of how cells dynamically respond to DNA nanostructures at nano- and micro- scale. We observe significant membrane deformation as a result of the binding of DNA nanostructures onto cell membranes, while remarkably, the overall cell viability remains largely unaffected throughout this process. This finding reinforces the potential of DNA nanostructures as promising candidates for cell membrane engineering and further applications. One potential category of the biomedical applications is to use DNA nanostructures as delivery vehicles for therapeutic agents. To enhance intracellular delivery, a cell-surface binding approach is employed. Compared to bare DNA nanostructures, cell-surface targeted structures demonstrate up to an 8-fold increase in intracellular delivery within just half an hour. Notably, the intranuclear delivery of these structures also experiences a remarkable up to 3-fold improvement. Such an enhancement is consistent across a diverse array of DNA nanostructures, such as DNA nanospheres, nanorods, and nanotiles, and utilizes various membrane attachment methods, including cholesterol membrane anchoring and click glyco- calyx anchoring. These findings pose DNA nanostructures as promising delivery systems for therapeutic agents, proteins, and even genetic material. Lastly, to showcase the potential of DNA nanostructures as a biomaterial for biomedical applications, we construct a synthetic cellular armor utilizing DNA nanorods to enhance the cellular protection against external threats. By recruiting and crosslinking DNA rods on the cell membrane, a versatile and programmable nanoshell is constructed, serving as a robust protective barrier that enhances cell viability when faced with environmental assaults. Interestingly, the nanoshell also exerts influence over the biophysical properties of the membrane, presenting itself as a platform for studying the relationship between membrane biomechanics and cell function.In conclusion, this thesis represents initial steps towards engineering cell membranes using structural DNA nanotechnology, from exploring the cellular response to DNA nanostructures, to leveraging membrane binding for rapid enhancement in the intracellular and intranuclear delivery, to using DNA as a protective biomaterial for cell encapsulation. By harnessing the potential of DNA-based nanoplatforms, we seek to understand how to better interact with cellular membranes, and contribute to new frontiers in membrane manipulation and pave the way for potential transformative advancements in biomedical science.

Subject Added Entry-Topical Term  

Mechanical engineering.

Subject Added Entry-Topical Term  

Biomedical engineering.

Subject Added Entry-Topical Term  

Nanotechnology.

Index Term-Uncontrolled  

Cell membranes

Index Term-Uncontrolled  

DNA nanostructures

Index Term-Uncontrolled  

Cell encapsulation

Added Entry-Corporate Name  

Carnegie Mellon University Mechanical Engineering

Host Item Entry  

Dissertations Abstracts International. 85-04B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:641683