The Petrie Dish
Featured Publications
See our most recent publications below. For individual Google Scholar profiles, see Personnel.
The role of dynamic reciprocity in 3D cell migration: connecting cell and matrix mechanics to migratory plasticity
While migratory cells can quickly change their mode of migration in complex three-dimensional environments, it is not clear why. Understanding the dynamic and reciprocal relationship migrating cells have with their microenvironments may help reveal why migratory plasticity, or mode-switching, is a common feature of eukaryotic cell motility. In this review, we discuss the physical and mechanical properties of cells and the environments they move through, and how those properties can influence each other. Given the dual role of the cytoskeleton in cell migration and cellular mechanics, we suggest that migratory plasticity derives from the necessity for the cell to maintain mechanical homeostasis in diverse physical environments.
Culturing and Imaging Glioma Stem Cells in 3D Collagen Matrices
Methods to maintain human glioma stem cells as neurosphere cultures and image their dynamic behavior in 3D collagen matrices are described. Additional approaches to monitor glioma stem cell differentiation into mesenchymal-type cells, along with example data are included. Together, these approaches enable glioma stem cell differentiation to be controlled while maintaining the cells in culture, as well as allowing cell dynamics to be captured and analyzed. These methods should be helpful for those seeking to understand the molecular mechanisms driving the invasion of glioma cells through three-dimensional environments. © 2023 Wiley Periodicals LLC.
Non-muscle myosin II and the plasticity of 3D cell migration
Confined cells migrating through 3D environments are also constrained by the laws of physics, meaning for every action there must be an equal and opposite reaction for cells to achieve motion. Fascinatingly, there are several distinct molecular mechanisms that cells can use to move, and this is reflected in the diverse ways non-muscle myosin II (NMII) can generate the mechanical forces necessary to sustain 3D cell migration. This review summarizes the unique modes of 3D migration, as well as how NMII activity is regulated and localized within each of these different modes. In addition, we highlight tropomyosins and septins as two protein families that likely have more secrets to reveal about how NMII activity is governed during 3D cell migration. Together, this information suggests that investigating the mechanisms controlling NMII activity will be helpful in understanding how a single cell transitions between distinct modes of 3D migration in response to the physical environment.
Plectin linkages are mechanosensitive and required for the nuclear piston mechanism of three-dimensional cell migration
Cells migrating through physiologically relevant three-dimensional (3D) substrates such as cell-derived matrix (CDM) use actomyosin and vimentin intermediate filaments to pull the nucleus forward and pressurize the front of the cell as part of the nuclear piston mechanism of 3D migration. In this study, we tested the role of the cytoskeleton cross-linking protein plectin in facilitating the movement of the nucleus through 3D matrices. We find that the interaction of F-actin and vimentin filaments in cells on 2D glass and in 3D CDM requires actomyosin contractility. Plectin also facilitated these interactions and interacts with vimentin in response to NMII contractility and substrate stiffness, suggesting that the association of plectin and vimentin is mechanosensitive. We find that this mechanosensitive plectin complex slows down 2D migration but is critical for pulling the nucleus forward and generating compartmentalized intracellular pressure in 3D CDM, as well as low-pressure lamellipodial migration in 3D collagen. Finally, plectin expression helped to polarize NMII to in front of the nucleus and to localize the vimentin network around the nucleus. Together, our data suggest that plectin cross-links vimentin and actomyosin filaments, organizes the vimentin network, and polarizes NMII to facilitate the nuclear piston mechanism of 3D cell migration.