Engineering Force-Triggered Self-Destructive Hydrogels and DNA-Integrated Matrices for 3D Cellular Mechanobiology Restricted; Files & ToC

Abstract

Hydrogels are widely utilized in biomedical and materials science applications due to their high water content, tunable mechanics, and biocompatibility. This dissertation explores the design and implementation of DNA-crosslinked tetrapolyethylene glycol (tPEG) hydrogels for force-responsive and cellular force measurement applications. We first introduce force-triggered self-destructive hydrogels (SDHs) that integrate DNA hairpins as mechanosensitive crosslinkers. These hydrogels undergo controlled degradation upon mechanical stress, leveraging CRISPR-Cas12a-mediated enzymatic cleavage to enable dynamic material disassembly. Next, we investigate the synthesis and characterization of DNA-linked tPEG hydrogels, which provide a robust, uniform network with predictable mechanical properties. These materials exhibit tunable stiffness and responsiveness, making them ideal for biomaterial applications. Finally, we develop a novel platform for measuring 3D cellular forces using DNA tension probes embedded within tPEG hydrogels. This system allows real-time, molecular-scale quantification of cellular forces in physiologically relevant 3D environments, overcoming the limitations of traditional 2D force measurement techniques. By integrating bioorthogonal crosslinking chemistry and DNA-based molecular force sensors, this research advances the development of hydrogels with precisely controlled mechanical properties and force-responsive behavior. The findings contribute to fundamental mechanobiology, smart biomaterials, and applications in tissue engineering, drug delivery, and mechanosensing.

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About this Dissertation

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School	Laney Graduate School
Department	Physics
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Chemistry, Biochemistry Engineering, Materials Science Chemistry, Polymer
Keyword	3D Printing DNA hydrogels 3D Cell culture PEG hydrogels Cas12a Biomaterials
Committee Chair / Thesis Advisor	Khalid Salaita, Emory University
Committee Members	Justin Burton, Emory University Eric Weeks, Emory University Laura Finzi, Emory University Yonggang Ke, Emory University

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