Section: Application Domains

Imaging and analysis of cytoskeleton dynamics during cell migration

The ability to migrate in space is among the most fundamental functions of eukaryotic cells and thus is one of the best-studied phenomena in biology. During embryonic development, cell movements result in a massive reorganization of the embryo, from a simple spherical ball of cells into a multi-layered organism; many of the cells at or near the surface of the embryo move to a new, more interior location. Moreover, inadequate or inappropriate migration of immune cells is also critically important for the delivery of protective immune responses to tissues and for wound healing. Finally, cell migration may facilitate the dissemination of tumor cells from primary tumor in blood (extravasation) and eventually the colonization of other organs and the formation of secondary tumors.

It has been established that the cytoskeleton, composed of actin filaments, microtubules and intermediate filaments (elongated structures with a diameter of a few dozens of nanometers), is essential for several cell mechanisms, including cell migration, cell division and molecule trafficking:

• i/ the actin filaments promote cell protrusion, adhesion and retraction;

• ii/ the microtubules are the support of molecule traffic and cell polarization;

• iii/ the intermediate filaments are hypothesized to control microtubule organization.

Nevertheless, the mechanical and chemical states of migrating cells under various external conditions remain largely unknown. In the last decade, high-resolution microscopy methods led to the discovery of novel aspects of cell migration. Most approaches and models are limited to migration in 2D, justified by the flatness of the cell-motile mechanisms. However, the mechanical patterns that govern migration in 2D models are often not essential for efficient migration in 3D. Accordingly, recent very challenging 3D models of cells moving on flat surfaces have begun to emerge. The key challenge, however, is to understand how a 3D motile cell crawls through the 3D extracellular matrix. Another issue is of course to measure and understand how membrane protrusion and retraction keep the cell in homeostasis, which of course relate to membrane traffic.

The objective of serpico is to develop high-end signal processing and computer vision tools to unfold the dynamical coordination of microtubules, actin filaments and intermediate filaments in 3D, involved in cell migration, cell division and how molecular trafficking is coordinated with cytoskeleton changes in these fundamental cellular functions.