title: Multiscale Cues Drive Collective Cell Migration.
abstract: 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.
authors.affiliation: Department of Bioengineering, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.|Department of Electrical and Computer Engineering, Seoul National University, Seoul 151-742, Korea.|Division of Scientific Instrumentation, Optical Instrumentation Development Team, The Korea Basic Science Institute, Daejeon 34133, Korea.
authors.forename: Ki-Hwan
authors.initials: KH
authors.lastname: Nam
authors.affiliation: Department of Bioengineering, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Wood
authors.affiliation: Department of Electrical and Computer Engineering, Seoul National University, Seoul 151-742, Korea.|Institutes of Entrepreneurial BioConvergence, Seoul National University, Seoul 151-744, South Korea.|Seoul National University Hospital Biomedical Research Institute, Seoul National University hospital, Seoul 110-744, South Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.|Masonic Cancer Center, and Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Paolo P
authors.initials: PP
authors.lastname: Provenzano
authors.affiliation: Department of Bioengineering, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Deok-Ho
authors.initials: DH
authors.lastname: Kim
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D015398:Signal Transduction