3d traction forces in cancer cell invasion三维牵引力量癌细胞的入侵.pdfVIP

3D Traction Forces in Cancer Cell Invasion 1 ¨ 1 1 2,3 1 Thorsten M. Koch *, Stefan Munster , Navid Bonakdar , James P. Butler , Ben Fabry 1 Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany, 2 Molecular Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, Massachusetts, United States of America, 3 Division of Sleep Medicine, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, United States of America Abstract Cell invasion through a dense three-dimensional (3D) matrix is believed to depend on the ability of cells to generate traction forces. To quantify the role of cell tractions during invasion in 3D, we present a technique to measure the elastic strain energy stored in the matrix due to traction-induced deformations. The matrix deformations around a cell were measured by tracking the 3D positions of fluorescent beads tightly embedded in the matrix. The bead positions served as nodes for a finite element tessellation. From the strain in each element and the known matrix elasticity, we computed the local strain energy in the matrix surrounding the cell. We applied the technique to measure the strain energy of highly invasive MDA- MB-231 breast carcinoma and A-125 lung carcinoma cells in collagen gels. The results were compared to the strain energy generated by non-invasive MCF-7 breast and A-549 lung carcinoma cells. In all cases, cells locally contracted the matrix. Invasive breast and lung carcinoma cells showed a significantly higher contractility compared to non-invasive cells. Higher contractility, however, was not universally associated with higher invasiveness. For instance, non-invasive A-43