Spatiotemporal visualization of cell membrane dynamics and protein colocalization reveals correlation between membrane dynamics and metastatic invasion

Invasive migration is an important cellular behavior that drives cancer metastasis, which increases the difficulty in treatment and results in poor clinical outcomes. Metastasis is comprised of a series of dynamic processes including cancer cell migration, spreading through circulation system and invasion into distant organs. However, visualization of these underlying steps of metastasis is lack. Although spatiotemporal measurements of cell motion dynamics have been well studied to identify different dynamic patterns, little work has been done to visualize how these dynamic patterns occur on migrating cells. Therefore, we develop spatiotemporal visualization tools to broaden the application of the existing dynamical cell analysis. For instance, we propose visualization techniques to classify the cell edge velocities into three states: protrusion, quiescence and retraction and then visualize when and where these three states of membrane dynamics happen on videos of migrating cells. We also create a semi-automatic tool to allow the users to select the ROIs from the correlation map and then plot the ROIs back onto the original cell migration video. These visualization tools help the biologists to better understand the abstract velocity heat maps in a user friendly way. Biologists can also take the advantage of selecting any ROI through these tools, which enables them to easily observe important migration regions. Furthermore, we investigate the correlation between cell membrane dynamics and subcellular proteins colocalization in a cancer model system and discovered a tight coupling between active membrane dynamics and periodic protein colocalizaiton. This active membrane and periodic colocalization pattern correlates with slower and less persistent migration in 3D collagen matrix.