Lmna knockout mouse embryonic fibroblasts are less contractile than their wild-type counterparts
| Autor: | Cvc Carlijn Bouten, Miriam A.F. Kamps, S Sandra Loerakker, Cwj Cees Oomens, Jlv Jos Broers, van Iaew Inge Loosdregt |
|---|---|
| Přispěvatelé: | Ondersteunend personeel ODB, Moleculaire Celbiologie, RS: GROW - R2 - Basic and Translational Cancer Biology, RS: CARIM - R2.10 - Mitochondrial disease, Soft Tissue Biomech. & Tissue Eng., Institute for Complex Molecular Systems |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
STRESS Actin Cytoskeleton/physiology Biochemistry Actins/physiology Extracellular matrix Mice Stress Fibers Fibroblasts/physiology Mechanotransduction Cells Cultured Tissue homeostasis Mice Knockout Genetics Microscopy Cultured Chemistry ALPHA-ACTININ MECHANOTRANSDUCTION Mouse Embryonic Stem Cells/physiology Mouse Embryonic Stem Cells DEFECTS Lamin Type A Cell biology Biomechanical Phenomena Actin Cytoskeleton Actinin alpha 1 Nuclear lamina Stress fiber MIGRATION Knockout Biophysics Fluorescence Focal adhesion Lamin Type A/deficiency NUCLEAR MECHANICS 03 medical and health sciences Journal Article EXTRACELLULAR-MATRIX Animals Actin Stress Fibers/physiology Fibroblasts Mechanical Actins 030104 developmental biology Microscopy Fluorescence TISSUE CELLS Stress Mechanical ACTIN CAP |
| Zdroj: | Integrative Biology, 9(8), 709-721. Oxford University Press Integrative Biology, 9(8), 709-721. Royal Society of Chemistry |
| ISSN: | 1757-9694 |
| Popis: | In order to maintain tissue homeostasis and functionality, adherent cells need to sense and respond to environmental mechanical stimuli. An important ability that adherent cells need in order to properly sense and respond to mechanical stimuli is the ability to exert contractile stress onto the environment via actin stress fibers. The actin stress fibers form a structural chain between the cells' environment via focal adhesions and the nucleus via the nuclear lamina. In case one of the links in this chain is missing or aberrant, contractile stress generation will be affected. This is especially the case in laminopathic cells, which have a missing or mutated form of the LMNA gene encoding for part of the nuclear lamina. Using the thin film method combined with sample specific finite element modeling, we quantitatively showed a fivefold lower contractile stress generation of Lmna knockout mouse embryonic fibroblasts (MEFs) as compared to wild-type MEFs. Via fluorescence microscopy it was demonstrated that the lower contractile stress generation was associated with an impaired actin stress fiber organization with thinner actin fibers and smaller focal adhesions. Similar experiments with wild-type MEFs with chemically disrupted actin stress fibers verified these findings. These data illustrate the importance of an organized actin stress fiber network for contractile stress generation and demonstrate the devastating effect of an impaired stress fiber organization in laminopathic fibroblasts. Next to this, the thin film method is expected to be a promising tool in unraveling contractility differences between fibroblasts with different types of laminopathic mutations. |
| Databáze: | OpenAIRE |
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