January 2019 : Cell shape changes and cytoskeleton adaptation to migrate into complex environments

Cell migration is an essential biological process that drives tissue and organ formation during embryo development, and also helps protect the body through immune response and wound healing mechanisms.

The shape changes necessary for cell migration depends on dynamic organization and force generation from the cell’s internal actomyosin cytoskeleton, which is made up of structural actin filaments and contractile myosin motor proteins. Reorganization of these components enables two mechanisms of cell migration; the growth and extension of actin-based lamellipoidal protrusion that allow the cell to ‘crawl’ outwards, or the formation of large contractile actomyosin cables that enable generation of traction forces onto the substrate. However, the process by which the cell chooses to form protrusions or contractile cables remains unclear.
Depending on the topography of the physical environment, cells may encounter regions of positive or negative curvature. Positive curvature refers to a convex shape that curves outward, much like a capital letter ‘D’, whereas an example of the opposite negative curvature can be seen in the letter ‘C’, which forms a concave shape that curves inward. By observing epithelial cell migration on flower-shaped substrate patterns that are used for wound closure assays, the research team Ladoux-Mège in collaboration with R. Voituriez (laboratoire Jean Perrin, CNRS and Sorbonne Paris Cité), The Mechanobiology Institute (Singapore), IBEC (spain) and Technion University (Israel) found that at regions of positive curvature, cells developed lamellipodia for cell crawling, and at regions of negative curvature, strong actin cables assembled that followed the concave edge.
Fortunately, the live cell imaging provided with the researchers with a potential clue – the switch in the direction of actin flow depending on curvature could potentially be the ‘sensor’ for switching the mode of migration. This study reveals how cells can sense larger cell-size curvature changes at a scale up to tens of micrometres, through dynamic adaptation of the actin flow. This ability allows the cell to select an appropriate mechanism to continue migration, even when faced with diverse changes in the physical environment, much like how an off road vehicle can switch between two- and four-wheel drive depending on the terrain. With the new knowledge of this actin flow switch, scientists may be better able to understand how cells can continue migration during wound healing, or in situations where migration can be damaging such as the metastatic progression of cancer.

Contact : Benoit Ladoux, team : "Cell Adhesion and Mechanics".

Go to top page