title: Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration.
abstract: Directed migration by contact guidance is a poorly understood yet vital phenomenon, particularly for carcinoma cell invasion on aligned collagen fibres. We demonstrate that for single cells, aligned architectures providing contact guidance cues induce constrained focal adhesion maturation and associated F-actin alignment, consequently orchestrating anisotropic traction stresses that drive cell orientation and directional migration. Consistent with this understanding, relaxing spatial constraints to adhesion maturation either through reduction in substrate alignment density or reduction in adhesion size diminishes the contact guidance response. While such interactions allow single mesenchymal-like cells to spontaneously 'sense' and follow topographic alignment, intercellular interactions within epithelial clusters temper anisotropic cell-substratum forces, resulting in substantially lower directional response. Overall, these results point to the control of contact guidance by a balance of cell-substratum and cell-cell interactions, modulated by cell phenotype-specific cytoskeletal arrangements. Thus, our findings elucidate how phenotypically diverse cells perceive ECM alignment at the molecular level.
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.|University of Minnesota Physical Sciences in Oncology Center, Minneapolis, Minnesota 55455, USA.
authors.forename: Arja
authors.initials: A
authors.lastname: Ray
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, Washington 98105, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Zaw
authors.initials: Z
authors.lastname: Win
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.|University of Minnesota Physical Sciences in Oncology Center, Minneapolis, Minnesota 55455, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Edwards
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.|University of Minnesota Physical Sciences in Oncology Center, Minneapolis, Minnesota 55455, USA.|Institute for Engineering in Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Alford
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, Washington 98105, USA.
authors.forename: Deok-Ho
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.|University of Minnesota Physical Sciences in Oncology Center, Minneapolis, Minnesota 55455, USA.|Institute for Engineering in Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.|Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Paolo P
authors.initials: PP
authors.lastname: Provenzano
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D016880:Anisotropy; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D000199:Actins