Title: Directed Migration of Mesenchymal Cells: By Compass or By Feel?

Abstract: Cell migration directed by spatial cues, or taxis, is a primary mechanism for orchestrating concerted and collective cell movements during development, wound repair, and immune responses. Compared with the classic example of amoeboid chemotaxis, in which fast-moving cells such as neutrophils are directed by gradients of soluble factors, directed migration of slow-moving mesenchymal cells such as fibroblasts is poorly understood. Mesenchymal cells possess a distinctive organization of the actin cytoskeleton and associated adhesion complexes as its primary mechanical system, generating the asymmetric forces required for locomotion without strong polarization; they also engage in other forms of directed migration, notably in response to gradients of extracellular matrix composition and stiffness. The emerging hypothesis is that the molecular underpinnings of mesenchymal taxis involve distinct signaling pathways and diverse requirements for regulation.

In this talk, I will discuss how we have used live-cell microscopy, computational image analysis, and physicochemical modeling to address the following questions in the context of mesenchymal cell migration:

How are new protrusions (lamellipodia) initiated and oriented, and how are they stabilized? How are protrusion dynamics governed on a longer time scale to affect directional persistence or reorientation of cell locomotion? What signaling and cytoskeletal mechanisms are required for mesenchymal chemotaxis, and are those determinants universal for other forms of directed migration?