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Exploring Structure and Mechanics of Molecular Sensors and DNA Nanodevices

Lopez, Diana
http://orcid.org/0000-0003-0817-6951
http://rave.ohiolink.edu/etdc/view?acc_num=osu1721373264214653

Abstract Details

2024, Doctor of Philosophy, Ohio State University, Biophysics.
Here we present investigations on the structure and mechanics of molecular force sensors and DNA nanodevices using a combination of computational and experimental approaches. This work implements a range of methods from all-atom and coarse-grained molecular dynamics to cryogenic and transmission electron microscopy. All-atom molecular dynamics simulations were employed to characterize the mechanical properties of peptide-based and DNA-based molecular force sensors. The simulations revealed that the stiffness of peptide-based sensors, derived from spider silk or synthetic peptides, is consistent with theoretical predictions and experimental measurements. However, the formation of transient secondary structures in spider silk-based sensors and overstretching in DNA-based sensors can influence their elastic responses, highlighting the importance of considering these factors in sensor design. The research also explored the use of DNA origami nanostructures for delivering gene templates for homology-directed repair (HDR) in human cells. Coarse-grained simulations (oxDNA) guided the design of DNA nanostructures, and experiments demonstrated their efficacy in enhancing HDR efficiency compared to unstructured DNA, particularly when delivered using Cas9 virus-like particles (VLPs). This finding suggests the potential of DNA nanostructures for targeted gene delivery and genome editing applications. Furthermore, the dissertation explored the development of DNA-origami-protein hybrid devices for cryogenic electron microscopy characterization of protein interactions and force spectroscopy applications. Preliminary data demonstrated the feasibility of integrating peptide-based force sensors into DNA nanostructures, which is a step toward enabling the real-time measurement of mechanical forces applied to proteins. These hybrid devices hold promise for studying protein mechanics, folding, and interactions at the nanoscale, with potential applications in biomedical research, for example to study how protein mechanics and interactions change with disease related mutations. Overall, this work contributes to the advancement of DNA nanotechnology and its applications in fields including molecular biophysics, gene delivery, and protein mechanics and biochemistry. The insights gained from the computational and experimental studies presented here can guide the design of more efficient molecular force sensors and DNA nanodevices, opening new avenues for research and therapeutic interventions.
Marcos Sotomayor (Advisor)
Carlos Castro (Advisor)
200 p.
Biophysics
Molecular dynamics simulations, molecular force sensors, DNA-origami, oxDNA, SMD simulations, force spectroscopy.

Recommended Citations

Citations

  • Lopez, D. (2024). Exploring Structure and Mechanics of Molecular Sensors and DNA Nanodevices [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1721373264214653

    APA Style (7th edition)

  • Lopez, Diana. Exploring Structure and Mechanics of Molecular Sensors and DNA Nanodevices . 2024. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1721373264214653.

    MLA Style (8th edition)

  • Lopez, Diana. "Exploring Structure and Mechanics of Molecular Sensors and DNA Nanodevices ." Doctoral dissertation, Ohio State University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=osu1721373264214653

    Chicago Manual of Style (17th edition)

osu1721373264214653
213
© 2024, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.