Contractile forces during cancer cell invasion

Abstract

Cell invasion through a dense 3-dimensional matrix is thought to depend on the force balance between the steric hindrance of the matrix on the one hand, and cell traction forces on the other hand. To quantify the role of cell tractions during invasion, we measured the strain energy of different invasive and non-invasive cancer cell lines. Cells were cultured in a 3-D reconstituted collagen gel (shear modulus G’=100 Pa, 500 μm thickness, average mesh size 1.6 μm). Within hours after seeding, cells started to contract and deform the collagen gel. The undeformed state of the gel was obtained after addition of the actin-disrupting drug cytochalasin- D. Gel deformations were measured by tracking the 3-D spatial positions of fluorescent beads (1 μm diameter) embedded in the gels before and after cytochalasin-D addition. The bead positions served as nodes for a finite element tessellation. From the local strain of each finite element and the elastic modulus of the collagen, we computed the local strain energy stored in the collagen gel surrounding the cell. The strain energy generated by invasive carcinoma cell lines was consistently high, on the order of 10 pJ, comparable to highly contractile smooth muscle cells. In some cases, however, the strain energy generated by non-invasive cells was even higher. Importantly, invasive cells assumed an elongated spindle-like morphology and generated a highly anisotropic strain field, whereas non-invasive cells displayed a rounder shape and an isotropic strain field. These results suggest that contractile forces of sufficient magnitude are essential for cancer cell invasion through a dense 3-D network, but in addition, the direction of traction generation is an important contributing factor.