Hs27 fibroblast response to contact guidance cues

Abstract

Contact guidance is the phenomena of how cells respond to the topography of their external environment. The morphological and dynamic cell responses are strongly influenced by topographic features such as lateral and vertical dimensions, namely, ridge and groove widths and groove depth (Rw,Gw,andGD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{R}}}_{{\ ext{w}}}, {{\ ext{G}}}_{{\ ext{w}}},\\,\\mathrm{and}\\,\\,{{\ ext{G}}}_{{\ ext{D}}}$$\\end{document}, respectively). However, experimental studies that independently quantify the effect of the individual dimensions as well as their coupling on cellular function are still limited. In this work, we perform extensive parametric studies in the dimensional space—well beyond the previously studied range in the literature—to explore topographical effects on morphology and migration of Hs27 fibroblasts via static and dynamic analyses of live cell images. Our static analysis reveals that the GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document} is most significant, followed by the Rw\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{R}}}_{{\ ext{w}}}$$\\end{document}. The fibroblasts appear to be more elongated and aligned in the groove direction as the GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document} increases, but their trend changes after 725 nm. Interestingly, the cell shape and alignment show a very strong correlation regardless of GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document}. Our dynamic analysis confirms that directional cell migration is also strongly influenced by the GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document}, while the effect of the Rw\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{R}}}_{{\ ext{w}}}$$\\end{document} and Gw\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{w}}}$$\\end{document} is statistically insignificant. Directional cell migration, as observed in the static cell behavior, shows the statistically significant transition when the GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document} is 725 nm, showing the intimate links between cell morphology and migration. We propose possible scenarios to offer mechanistic explanations of the observed cell behavior.