Funded projects

Mechanical modification of collagen gels by single cells and spheroids

2013 - T. Betz, D. Vignjevic (UMR144)

One of the main problems in cancer is the formation of metastasis that invade the remaining body. During this process, cancer cells migrate out of the tumor and move through the neighboring tissue, which is mainly made up of collagen forming the so-called extra-cellular-matrix. Despite its importance the process of invasion is far from being understood and especially how the mechanical properties might influence the invasion remains unclear. During this scientific cooperation, we will combine the cell biological and physics approaches to study if the tumor itself modifies the mechanical properties of its environment, and if this facilitates the conditions for invasion.

Funded Research project 4

(upper panel) Spheroid of cancer cells embedded in a collagen I matrix.
(lower panel) Deformation of the collagen matrix (blue 0, red 5 µm/h). The cells outlines are marked by the black line. The anisotropic outgrowth correlates with the gel contraction.

In preliminary experiments we have observed that a spheroid of cancer cells (which mimics a tumor), embedded in a collagen matrix (which mimics the extra-cellular-matrix) first start to mechanically contract the collagen in a radial way (see illustration), before the cancer cells start to migrate outward, and hence invade the environment. Our working hypothesis is that the contraction which is maintained by the cancer cells stiffens the collagen matrix until the environment provides enough mechanical support for migration. During our collaboration we will test this hypothesis by direct measurements of the collagen elasticity before and during invasion. Furthermore, we will use UV-micro-ablation and external deformation to mimic or to compensate the contraction of the collagen by the cancer cells. These experiments will give direct evidence if the contraction stimulates mechanical changes that then lead to the onset of invasion in the model system.