title: Cellular strain avoidance is mediated by a functional actin cap - observations in anLmna-deficient cell model.
abstract: In adherent cells, the relevance of a physical mechanotransduction pathway provided by the perinuclear actin cap stress fibers has recently emerged. Here, we investigate the impact of a functional actin cap on the cellular adaptive response to topographical cues and uniaxial cyclic strain.Lmna-deficient fibroblasts are used as a model system because they do not develop an intact actin cap, but predominantly form a basal layer of actin stress fibers underneath the nucleus. We observe that topographical cues induce alignment in both normal andLmna-deficient fibroblasts, suggesting that the topographical signal transmission occurs independently of the integrity of the actin cap. By contrast, in response to cyclic uniaxial strain,Lmna-deficient cells show a compromised strain avoidance response, which is completely abolished when topographical cues and uniaxial strain are applied along the same direction. These findings point to the importance of an intact and functional actin cap in mediating cellular strain avoidance.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, Eindhoven 5600 MB, The Netherlands.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tamiello
authors.affiliation: Department of Molecular Cell Biology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands.
authors.forename: Maurice
authors.initials: M
authors.lastname: Halder
authors.affiliation: Department of Molecular Cell Biology, GROW - School for Oncology & Developmental Biology, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands.
authors.forename: Miriam A F
authors.initials: MA
authors.lastname: Kamps
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, Eindhoven 5600 MB, The Netherlands.|Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, Eindhoven 5600 MB, The Netherlands.
authors.forename: Frank P T
authors.initials: FP
authors.lastname: Baaijens
authors.affiliation: Department of Molecular Cell Biology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands.
authors.forename: Jos L V
authors.initials: JL
authors.lastname: Broers
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, Eindhoven 5600 MB, The Netherlands c.v.c.bouten@tue.nl.
authors.forename: Carlijn V C
authors.identifier: 0000-0003-1035-5094
authors.initials: CV
authors.lastname: Bouten
mesh_terms: D000185:Actinin; D000199:Actins / Q000378:metabolism*; D000818:Animals; D016880:Anisotropy; D048430:Cell Shape; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D034904:Lamin Type A / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D022502:Stress Fibers / Q000378:metabolism; D013314:Stress, Mechanical; D013312:Stress, Physiological; D013997:Time Factors
chemical_list: D000199:Actins; C491752:Actn4 protein, mouse; D034904:Lamin Type A; D000185:Actinin; D009218:Myosins
keywords: Cell orientation; Cyclic strain; Lmna-lacking cells; Mechanotransduction; Stress fibers; Substrate topography