ABSTRACT
Extracellular forces transmitted through the cytoskeleton can deform the cell nucleus. Large nuclear deformations increase the risk of disrupting the integrity of the nuclear envelope and causing DNA damage. The mechanical stability of the nucleus defines its capability to maintain nuclear shape by minimizing nuclear deformation and allowing strain to be minimized when deformed. Understanding the deformation and recovery behavior of the nucleus requires characterization of nuclear viscoelastic properties. Here, we quantified the decoupled viscoelastic parameters of the cell membrane, cytoskeleton, and the nucleus. The results indicate that the cytoskeleton enhances nuclear mechanical stability by lowering the effective deformability of the nucleus while maintaining nuclear sensitivity to mechanical stimuli. Additionally, the cytoskeleton decreases the strain energy release rate of the nucleus and might thus prevent shape change-induced structural damage to chromatin.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: X.W., H.L., C.C., T.F., Y.S.; Methodology: X.W., H.L., C.C., Z.X., Y.T., H.M.; Software: X.W.; Validation: X.W., H.L., C.C., Z.X., C.K.; Formal analysis: X.W.; Investigation: X.W., H.L., M.Z.; Resources: X.W., H.L.; Data curation: X.W., M.Z., K.L.; Writing - original draft: X.W.; Writing - review & editing: H.L., T.F., H.M., C.A.S., S.H., Y.S.; Visualization: X.W., Z.X., Y.T., K.L.; Supervision: H.M., C.A.S., S.H., Y.S.; Project administration: X.W., S.H., Y.S.; Funding acquisition: H.M., Y.S.
Funding
This work was supported by the Natural Sciences and Engineering Research Council of Canada via an NSERC Steacie Memorial Fellowship, the Canada Research Chairs program and the Canadian Institutes of Health Research (143319 to H.M.).
Data availability
The AFM datasets, microscope images and custom-made code for data analysis are available through the link https://github.com/XianShawn/Nuclear_Mechanics. The MATLAB code is for the purpose of reproducible research and not for commercial usage. The other data that support the findings of this study are available from the corresponding author upon reasonable request.
Supplementary information
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.209627.supplemental
- Received August 15, 2017.
- Accepted May 14, 2018.
- © 2018. Published by The Company of Biologists Ltd