Organoids to Organisms: Engineering 3D Microenvironments to Support Biological Systems
- Rosas, Jonah Mathew
- Advisor(s): Pitenis, Angela A;
- Montell, Denise J
Abstract
The microenvironment plays a central role in supporting a diverse set of cell functions ranging from cell fate decisions that specify cell lineage during early embryonic development to single-cell and organ-scale size regulation. In the past two decades, a renewed emphasis has been placed on the mechanical microenvironment and its role in healthy and disease biology.
In this dissertation, I describe the rheology of granular, polyacrylamide hydrogels composed of micron-scale fragments, herein referred to as microgels, and demonstrate their utility in supporting the extended imaging of the model organism danio renio (zebrafish) and for controlling the mechanical microenvironment encapsulating pancreatic ductal adenocarcinoma organoids. This work addresses two long standing challenges in the field: 1) Microgels offer an engineered embedding method that extends zebrafish embryonic imaging times by 8 compared to field standards. 2) Pancreas ductal adenocarcinoma (PDAC) organoids exhibit an emergent pulsing behavior that is enhanced in confining microgel environments, suggesting the underlying genetics of tumor cells give rise to force generating behaviors that may be assistive for adaptation to highly fibrotic tumor microenvironments in vivo.