Biomimetism of cellular movement
Cécile Sykes and Julie Plastino
Keywords: Biomimetic systems, cell motility, cell shape, actin cytoskeleton, myosin, membranes, C. elegans, cancer cell invasion and metastasis, asymmetric cell division
The ultimate goal of our work is to understand how cells change shape and move, with implications for understanding cancer invasion and metastasis. We use biomimetic systems and simple cellular and animal models to study cell shape change under controlled conditions. Using such approaches, we can dissect the physical and biochemical mechanisms governing cell shape change and movement.
In the past we have successfully mimicked actin-based propulsion, where actin polymerization is reproduced in a controlled fashion on surfaces by attaching actin polymerization activators. These surfaces include hard beads, soft beads and inner or outer leaflets of lipid bilayers of liposomes. The objects are then incubated in cell extracts or in pure protein mixes and the actin structures that grow from the surfaces mimic the cellular actin cytoskeleton. This set-up lends itself to quantitative measurements of the mechanism of cell cytoskeleton assembly and its mechanics. We are now developing systems with molecular motors and membranes that reproduce cell shape changes and cortical acto-myosin dynamics. For example the addition of myosin motors to the actin network next to a liposome membrane reproduces cell tension that can be quantified using liposome doublets (Figure 1).
Figure 1: A liposome doublet is covered with actin filaments and myosin motors and reproduces tension build up in cells. Its change in shape (flattening of the angle between the two liposomes) allows for an estimation of the produced tension.
In parallel with our work on reconstituted systems, we study similar acto-myosin structures in simple in vivo models, including cells in culture, mouse oocytes, nematode embryos and the anchor cell during basement membrane invasion in Caenorhabditis elegans (Figure 2). In all cases, we examine how the biochemistry of actin assembly affects force generation and myosin activity, and how individual filament dynamics are integrated to produce overall cell shape changes during cell division, embryogenesis and development.
Figure 2: Anchor cell invasion in C. elegans development. Side view of the developing worm. The anchor cell (inset, green) forces its way through a basement membrane (inset, red), employing proteases and actin polymerization to make a hole that becomes the worm vulva. DIC and epifluorescence microscopy.