Cancer cell invasion is a highly orchestrated and complex biological process, which is influenced by a plethora of biophysical and biochemical signals that emerge from the tumor microenvironment. In this project, a team of bioengineers, physicists and cancer biologists aim to develop an innovative platform technology to study the dynamic alterations in breast cancer cells and tumor microenvironment during disease progression. The proposed platform technology is comprised of a tumor model integrated with advanced imaging and measurement techniques. Insight from this research will significantly benefit society in terms of advancing our fundamental understanding of cancer progression to an invasive state. Furthermore, the proposed research plan will provide a foundation for a highly collaborative and teamwork oriented environment to engage students and researchers in science and engineering.
The goal of this project is to develop a novel three-dimensional (3D) microengineered breast tumor model integrated with nanoscale force tomography technique to assess the mechanobiological changes that the cancer cells and their surrounding matrix undergo during tumor progression. By successfully building upon the diseased tissue model, the first objective of this research is to determine whether the biophysical properties of the tumor extracellular matrix, in presence of stromal components, are sufficient to promote cancer cell invasion. The second objective is to determine the dynamic changes in the biomechanical properties of cancer cells, while penetrating through the tumor tissue. Furthermore, this study aims at drawing a direct correlation between the geometrical features of the primary tumor region, invasive activity and biomechanical properties of cancer cells. Novel features of the proposed tumor model include that it is modular and that it enables decoupling and analyzing the effect of various microenvironmental cues on cancer cell invasion. Although this interdisciplinary research focuses on breast cancer, the 3D diseased tissue model along with the quantitative measurement technique is versatile and can be used for studies on other types of cancer as well. In addition, the proposed platform technology has a broad impact to investigate other biological processes related to cell migration and biophysics. With respect to the educational impact, this study will provide a solid foundation for interdisciplinary training in the areas of microscale technologies, tissue engineering and cell biophysics to high school, undergraduate and graduate students.
