Vishwa Vasani
BioE PhD Défense Presentation
Monday April 14th, 2 PM
IBB Room 1128 (Suddath seminar room)
Online link: https://teams.microsoft.com/l/meetup-join/19%3ameeting_OWJiYWEyZDgtZjBkYy00OGNmLWJhY2YtZjMzYmUyY2JmNzEz%40thread.v2/0?context=%7b%22Tid%22%3a%22482198bb-ae7b-4b25-8b7a-6d7f32faa083%22%2c%22Oid%22%3a%22a4eb64bb-1df9-440d-a626-d9ebe6922c6a%22%7d
Advisor:
Dr. Shuichi Takayama, Wallace H. Coulter Department of Biomedical Engineering
Committee:
Dr. Andrés García, George Woodruff School of Mechanical Engineering
Dr. Yesim Gokmen-Polar, Emory University, Department of Pathology and Laboratory Medicine
Dr. Todd Sulchek ,George Woodruff School of Mechanical Engineering
Dr. Cheng Zhu, Wallace H. Coulter Department of Biomedical Engineering
Mechanical Characterization of Microengineered Models
Organoids have gained increased interest in recent years as promising platforms for preclinical testing of anticancer drugs and modeling disease progression, offering key advantage of posessing native tissue-like architecture and incorporating Cell-ECM interactions over the other in-vitro model systems. Cancer cell behavior is known to be sensitive to extracellular matrix, so when organoids are developed as an anticancer drug screening platform, it is useful to characterize the matrisome following dynamic alteration by the cells comprising the organoid and comparing to in-vivo tumor tissue. In this work, we take a detailed look into the stably inverted mammary organoid platform developed previously to model breast cancer development and compare culture conditions that have different susceptibilities to cancer cell invasion. From bulk RNA sequencing, we find that the key processes to have different gene expression levels between these culture conditions are related to producing and remodeling the ECM. From ECM-enriched proteomics analysis of organoids, we find that the constituent epithelial cells significantly modify the organoid matrisome in a time-dependent manner. Comparing differentially matured organoids by ECM proteomics, transcriptomics and micropipette aspiration-based mechanical characterization, we find a unique matrisome signature in younger organoids which is stiffer, more EMT-promoting and more pro-tumorigenic than mature organoids. Additionally, we also discuss the development of a microfluidic micropipette aspiration technique for characterizing epithelial organoids. Specifically, we develop a mechanical model that considers the architecture of epithelial organoids when describing their pressure-deformation relationship. Further, we describe in detail an experimental setup for microfluidic micropipette aspiration of organoids. We then perform experimental measurements to verify the validity of the model developed. In other work, we also develop a mechanistic framework for modeling pneumatic control mechanisms integrated into microfluidic systems. We perform a mathematical and experimental investigation of gas-driven microfluidic circuits, focusing on forced-air oscillators. We derive and validate a first-principles model of microfluidic circuit elements operated under positive pressurization. Our findings reveal that gas compressibility impacts circuit behavior by acting similar to a large capacitor in the system, which inherently results in longer oscillation periods, which then reduce as the syringe empties.