Analysis of cell migration in vivo combined with biophysical measurements reveals how membrane-to-cortex attachment fine-tunes the type of protrusions formed by cells and, as a consequence, controls directed migration during zebrafish gastrulation.
Cell shape and motility are primarily controlled by cellular mechanics. The attachment of the plasma membrane to the underlying actomyosin cortex has been proposed to be important for cellular processes involving membrane deformation. However, little is known about the actual function of membrane-to-cortex attachment (MCA) in cell protrusion formation and migration, in particular in the context of the developing embryo. Here, we use a multidisciplinary approach to study MCA in zebrafish mesoderm and endoderm (mesendoderm) germ layer progenitor cells, which migrate using a combination of different protrusion types, namely, lamellipodia, filopodia, and blebs, during zebrafish gastrulation. By interfering with the activity of molecules linking the cortex to the membrane and measuring resulting changes in MCA by atomic force microscopy, we show that reducing MCA in mesendoderm progenitors increases the proportion of cellular blebs and reduces the directionality of cell migration. We propose that MCA is a key parameter controlling the relative proportions of different cell protrusion types in mesendoderm progenitors, and thus is key in controlling directed migration during gastrulation.
Cell migration, like any event involving shape changes, is a mechanical process controlled by complex biochemical pathways. Here, we examine cell migration in developing embryos with a combination of cell biological tools and atomic force microscopy, so as to investigate how cellular mechanical properties control migration. A fundamental step during migration is the formation of a protrusion at the leading edge of the cell. In three-dimensional environments, and particularly in vivo, cells use different protrusion types: spike-like filopodia and flattened lamellipodia, whose growth is driven by actin polymerization, and spherical blebs, which grow because of intracellular pressure pushing on the membrane. It is important to understand how the formation of different protrusion types is mechanically and molecularly controlled, and how the different protrusions specifically contribute to migration. We have addressed this using the zebrafish embryo as a model system. We show that reducing the strength of the attachment between the plasma membrane and the underlying cortical network of actin filaments, or increasing intracellular pressure, increases the proportion of cellular blebs and reduces the directionality of cell migration. Our work reveals that blebs, lamellipodia, and filopodia are not interchangeable and that the relative proportion of each type of protrusion, under the control of mechanical parameters, determines migration directionality during zebrafish gastrulation.