Research Projects

Cancer metastasis is a complex process that presents significant challenges to current cancer treatments. It occurs when cancer cells detach from the primary tumor and invade distant tissues. This transition from a nonmotile to a motile state requires a series of biological, chemical, and physical changes. While the biochemical pathways promoting motility in cancer cells are well-documented, the role of biomechanical forces in driving metastasis has gained attention only recently. Studies show that cancer cells exhibit altered mechanical properties, including cellular tension, hydrostatic pressure, and adhesion forces. These changes also influence the mechanical properties of the surrounding tissue, affecting its elasticity and viscosity. Tumor progression involves intracellular and intercellular reorganization as well as remodeling of the extracellular matrix (ECM). ECM remodeling alters the tumor microenvironment’s physical properties, such as stiffness and network configuration, promoting malignant tumor phenotypes. Understanding how these mechanical changes impact tumor cell migration is critical for developing strategies to inhibit metastasis. For example, tumor cell-cell adhesion has been shown to increase under compressive stress from the ECM, a response not observed in normal cells. However, the interplay among differential adhesion, ECM stiffness, and their collective influence on tumor invasion remains poorly understood. Most existing studies focus on two-dimensional (2D) models of ECM-tumor cell interactions, leaving a significant gap in research on 3D models that capture the complexity of the ECM-tumor microenvironment. Recognizing the natural 3D environment of tissues, we will employ a state-of-the-art 3D vertex model to study cancer cell migration within explicit ECM networks. This computational approach will address the critical challenge of identifying factors contributing to the “fluidization” of cancer cells, enabling them to overcome the mechanical barriers of their microenvironment. We will investigate how intra-tumoral mechanical heterogeneity—where cells have varying stiffness—affects cell migration. These findings will provide predictive insights into tumor behavior and aggressiveness, enhancing diagnostic and prognostic evaluations. Additionally, we will explore how ECM properties such as density, stiffness, and alignment influence tumor cell migration in 3D. To complement this, we will develop a computational model to simulate tumor cell growth (cell division) within the 3D vertex framework. This model will allow us to analyze how tumor growth affects the mechanical properties of both individual cells and the surrounding tissues, providing insights into the dynamic changes in tissue stiffness and structure during tumor progression. Understanding these biomechanical factors is essential for accurately modeling the tumor microenvironment (TME) and identifying mechanisms that could be targeted for therapeutic intervention.