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

Rajasooriya, Tharindu (Summer 2025)

Permanent URL: https://etd.library.emory.edu/concern/etds/fq977w32n?locale=zh
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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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