title: Keratins significantly contribute to cell stiffness and impact invasive behavior.
abstract: Cell motility and cell shape adaptations are crucial during wound healing, inflammation, and malignant progression. These processes require the remodeling of the keratin cytoskeleton to facilitate cell-cell and cell-matrix adhesion. However, the role of keratins for biomechanical properties and invasion of epithelial cells is only partially understood. In this study, we address this issue in murine keratinocytes lacking all keratins on genome engineering. In contrast to predictions, keratin-free cells show about 60% higher cell deformability even for small deformations. This response is compared with the less pronounced softening effects for actin depolymerization induced via latrunculin A. To relate these findings with functional consequences, we use invasion and 3D growth assays. These experiments reveal higher invasiveness of keratin-free cells. Reexpression of a small amount of the keratin pair K5/K14 in keratin-free cells reverses the above phenotype for the invasion but does not with respect to cell deformability. Our data show a unique role of keratins as major players of cell stiffness, influencing invasion with implications for epidermal homeostasis and pathogenesis. This study supports the view that down-regulation of keratins observed during epithelial-mesenchymal transition directly contributes to the migratory and invasive behavior of tumor cells.
authors.affiliation: Translational Center for Regenerative Medicine and Institute of Biology, and Fakultät für Physik und Geowissenschaften, Abteilung Physik der Weichen Materie, Universität Leipzig, 04103 Leipzig, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Seltmann
authors.forename: Anatol W
authors.initials: AW
authors.lastname: Fritsch
authors.forename: Josef A
authors.initials: JA
authors.lastname: Käs
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Magin
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology*; D003114:Colony-Forming Units Assay; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005818:Genetic Engineering / Q000379:methods; D007211:Indoles; D007633:Keratins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D012867:Skin / Q000166:cytology*; D016596:Vinculin
chemical_list: D007211:Indoles; D016596:Vinculin; C007293:DAPI; D007633:Keratins
keywords: Boyden chamber; cell mechanics; intermediate filaments; optical stretcher