Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep29749
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Funding
- FHCRC/UW Cancer Consortium Cancer Center Support Grant of the National Institutes of Health [P30CA015704]
- American Cancer Society [RSG-14-171-01-CSM]
- College of Science and Engineering and the Masonic Cancer Center of the University of Minnesota
- University of Minnesota Institute for Engineering in Medicine
- NIH National Cancer Institute [R01CA181385, P50CA101955]
- Randy Shaver Research and Community Fund
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2015K1A4A3047345]
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To investigate complex biophysical relationships driving directed cell migration, we developed a biomimetic platform that allows perturbation of microscale geometric constraints with concomitant nanoscale contact guidance architectures. This permits us to elucidate the influence, and parse out the relative contribution, of multiscale features, and define how these physical inputs are jointly processed with oncogenic signaling. We demonstrate that collective cell migration is profoundly enhanced by the addition of contract guidance cues when not otherwise constrained. However, while nanoscale cues promoted migration in all cases, microscale directed migration cues are dominant as the geometric constraint narrows, a behavior that is well explained by stochastic diffusion anisotropy modeling. Further, oncogene activation (i.e. mutant PIK3CA) resulted in profoundly increased migration where extracellular multiscale directed migration cues and intrinsic signaling synergistically conspire to greatly outperform normal cells or any extracellular guidance cues in isolation.
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