UNS: Three Dimensional Microengineered Diseased Tissue Model to Study Invasive Phenotype of Cancer Cells

肿瘤细胞侵袭是一个高度协调和复杂的生物学过程，受肿瘤微环境中产生的大量生物物理和生化信号的影响。在这个项目中，一个由生物工程师、物理学家和癌症生物学家组成的团队旨在开发一种创新的平台技术来研究乳腺癌细胞和肿瘤微环境在疾病进展过程中的动态变化。所提出的平台技术由肿瘤模型与先进的成像和测量技术相结合组成。从这项研究中获得的见解将大大有利于社会，促进我们对癌症进展到侵袭状态的基本理解。此外，拟议的研究计划将为高度协作和团队合作的环境提供基础，以吸引学生和研究人员参与科学和工程。该项目的目标是开发一种新型的三维（3D）微工程乳房肿瘤模型，结合纳米级力断层扫描技术来评估癌细胞及其周围基质在肿瘤进展过程中所经历的机械生物学变化。通过成功建立病变组织模型，本研究的第一个目标是确定肿瘤细胞外基质的生物物理特性，在基质成分存在的情况下，是否足以促进癌细胞的侵袭。第二个目标是确定癌细胞穿透肿瘤组织时生物力学特性的动态变化。此外，本研究旨在绘制原发肿瘤区域的几何特征、侵袭活性和癌细胞的生物力学特性之间的直接关系。所提出的肿瘤模型的新特点包括它是模块化的，它可以解耦和分析各种微环境线索对癌细胞侵袭的影响。虽然这项跨学科的研究主要集中在乳腺癌，但三维病变组织模型以及定量测量技术是通用的，也可以用于其他类型癌症的研究。此外，所提出的平台技术对研究与细胞迁移和生物物理学相关的其他生物过程具有广泛的影响。在教育影响方面，本研究将为高中生、本科生和研究生在微尺度技术、组织工程和细胞生物物理学领域的跨学科培训提供坚实的基础。

PI: Nikkhah, Mehdi Proposal Number: 1510700Cancer 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.