Project Summary Cancer metastasis accounts for over 90% of all cancer deaths. Important abilities of metastatic tumor cells include breaking away from the primary tumor and invading into surrounding tissue before disseminating to secondary tumor sites. Solid tumor stress caused by rapid growth of tumor cells and abnormality of the vascular tissue has long been associated with poor prognosis of cancer. Despite the clinical importance, the basic understanding of tumor mechanics and its relation to tumor invasion is lacking. This is in part due to the lack of in vitro tools that are able to investigate quantitatively tumor mechanics in a physiologically relevant 3D setting. Current material mechanical testing tools such as the rheometer have played important roles in our current understanding of biomaterials and tumor mechanics. However, the conventional rheometer is not easily made compatible with cell culture conditions and results are spatially averaged, masking important single cell and molecular level information. Atomic force microscopy and pipette aspiration are cell culture compatible, but low throughput. The goal of the proposed research is to develop a high throughput microfluidic rheometer for systematic studies of tumor mechanics and invasion in a physiologically realistic 3D setting and compatible with dynamic optical imaging at single cell and spheroid levels. We will deliver a set of principles that govern tumor mechanics and its relation with invasion. We postulate that tumor mechanics is a key predictor for tumor invasiveness. The proposed project is innovative because it represents the first generation of microfluidic rheometers that are capable of full mechanical testing for tumor mechanics studies, and at the same time compatible with tumor invasion experiments. Tools developed here can be easily extended to use for other living materials, and lessons learned here will eventually lead to knowledge important for developing novel diagnostic or/and treatment strategies for cancer.

Project Narrative The proposed project will develop an advanced mechanical testing tool for tumor mechanics studies. Knowledge learned in this proposal provides information that will aid in developing novel diagnostic or/and treatment strategies for cancer.