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

L. J. Kaufman  , C. P. Brangwynne ^*, K. E. Kasza ^*, E. Filippidi ^*, V. D. Gordon , T. S. Deisboeck  ^¶ and D. A. Weitz ^* 

^* Division of Engineering and Applied Sciences, and Department of Physics, Harvard University, Cambridge, Massachusetts; Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts; Center for Imaging and Mesoscale Structures, Harvard University, Cambridge, Massachusetts; and ^¶ Complex Biosystems Modeling Laboratory, Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts

Correspondence: Address reprint requests to Laura Kaufman, Dept. of Chemistry, Columbia University, New York, NY 10027. E-mail: kaufman{at}chem.columbia.edu.

We 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.

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