Metastasis is the cause of 90% of cancer-related deaths and yet the precise mechanism of metastasis is poorly understood[1]. To metastasize, cells break free from the primary tumor, migrate through the surrounding tissue, and enter the vascular system to move to a secondary site. To migrate through the stroma, cell can both degrade the tissue and use physical force to move the tissue from its path. However, the relative roles of matrix degradation and cellular force are not well-understood. Previous work has shown that as cell move through the matrix, they create channels that other cells can then use to more easily escape from the primary tumor [2, 3]. To investigate the mechanisms by which metastatic cells move through 3D matrices, we fabricated microchannels from collagen that simulate the paths that are made and used by cells during metastasis. Here, we will present our method for molding channels in compliant collagen gels to investigate cell migration. The channels dimensions approximate the size of a cell and permit cell migration without the need for matrix degradation. We demonstrate that the channels cause persistent, unidirectional cell migration that is significantly faster than the migration observed in 3D matrices without channels. These channels provide a unique platform to probe 3D cellular migration and permit the dissection of the relative roles of matrix degradation and force generation in facilitating cell invasion.

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