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https://doi.org/10.1371/journal.pone.0031320
Title: | The mechanical behavior of mutant K14-R125P keratin bundles and networks in NEB-1 keratinocytes | Authors: | Beriault D.R. Haddad O. McCuaig J.V. Robinson Z.J. Russell D. Lane E.B. Fudge D.S. |
Keywords: | F actin K14 protein keratin latrunculin A unclassified drug actin cytokeratin 14 green fluorescent protein hybrid protein KRT14 protein, human mutant protein article cell structure cell survival cell viability controlled study cytoskeleton epidermolysis bullosa simplex human human cell keratinocyte mechanical stress microtubule osmotic stress protein assembly protein expression Western blotting amino acid substitution biomechanics cell line chemistry cytoskeleton fluorescence microscopy genetics metabolism osmotic pressure pathology protein quaternary structure Actins Amino Acid Substitution Biomechanics Blotting, Western Cell Line Cell Survival Cytoskeleton Epidermolysis Bullosa Simplex Green Fluorescent Proteins Humans Keratin-14 Keratinocytes Microscopy, Fluorescence Microtubules Mutant Proteins Osmotic Pressure Protein Structure, Quaternary Recombinant Fusion Proteins Stress, Mechanical |
Issue Date: | 2012 | Citation: | Beriault D.R., Haddad O., McCuaig J.V., Robinson Z.J., Russell D., Lane E.B., Fudge D.S. (2012). The mechanical behavior of mutant K14-R125P keratin bundles and networks in NEB-1 keratinocytes. PLoS ONE 7 (2) : e31320. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0031320 | Rights: | Attribution 4.0 International | Abstract: | Epidermolysis bullosa simplex (EBS) is an inherited skin-blistering disease that is caused by dominant mutations in the genes for keratin K5 or K14 proteins. While the link between keratin mutations and keratinocyte fragility in EBS patients is clear, the exact biophysical mechanisms underlying cell fragility are not known. In this study, we tested the hypotheses that mutant K14-R125P filaments and/or networks in human keratinocytes are mechanically defective in their response to large-scale deformations. We found that mutant filaments and networks exhibit no obvious defects when subjected to large uniaxial strains and have no negative effects on the ability of human keratinocytes to survive large strains. We also found that the expression of mutant K14-R125P protein has no effect on the morphology of the F-actin or microtubule networks or their responses to large strains. Disassembly of the F-actin network with Latrunculin A unexpectedly led to a marked decrease in stretch-induced necrosis in both WT and mutant cells. Overall, our results contradict the hypotheses that EBS mutant keratin filaments and/or networks are mechanically defective. We suggest that future studies should test the alternative hypothesis that keratinocytes in EBS cells are fragile because they possess a sparser keratin network. © 2012 Beriault et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161999 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0031320 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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