Glioma Expansion in Collagen I Matrices: Analyzing Collagen Concentration-Dependent Growth and Motility Patterns

Kaufman, L. J., C. P. Brangwynne, K. E. Kasza, E. Filippidi, V. D. Gordon, T. S. Deisboeck, and D. A. Weitz. “Glioma Expansion in Collagen I Matrices: Analyzing Collagen Concentration-Dependent Growth and Motility Patterns.” Biophysical Journal 89, no. 1 (July 2005): 635–50. doi:10.1529/biophysj.105.061994. -- C. P. Brangwynne, K. E. Kasza, and E. Filippidi, are with the Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts -- L. J. Kaufman, V. D. Gordon (currently with UT Austin), and D. A.Weitz are with the Department of Physics, Harvard University, Cambridge, Massachusetts -- T. S. Deisboeck is with the Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts and {Complex Biosystems Modeling Laboratory, Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts -- L. J. Kaufman is with the Center for Imaging and Mesoscale Structures, Harvard University, Cambridge, Massachusetts; andWe study the growth and invasion of glioblastoma multiforme (GBM) in three-dimensional collagen I matrices of varying collagen concentration. Phase-contrast microscopy studies of the entire GBM system show that invasiveness at early times is limited by available collagen fibers. At early times, high collagen concentration correlates with more effective invasion. Conversely, high collagen concentration correlates with inhibition in the growth of the central portion of GBM, the multicellular tumor spheroid. Analysis of confocal reflectance images of the collagen matrices quantifies how the collagen matrices differ as a function of concentration. Studying invasion on the length scale of individual invading cells with a combination of confocal and coherent anti-Stokes Raman scattering microscopy reveals that the invasive GBM cells rely heavily on cell-matrix interactions during invasion and remodeling.Chemistr