ORCID
Sarthak Gupta: 0000-0002-3950-7955
Alison E. Patteson: 0000-0002-4004-1734
J. M. Schwarz: 0000-0001-9880-9999
Document Type
Article
Date
Fall 9-29-2021
Keywords
cell motility in confinement, cell polarity in confinement, vimentin, cytoskeleton, cell nucleus
Language
English
Funder(s)
National Science Foundation, National Institutes of Health, Isaac Newton Award, Syracuse University CUSE Grant and a Syracuse BioInspired Grant
Funding ID
NSF-DMR-1832002, DoD, NIH R35 GM142963
Acknowledgements
The authors acknowledge helpful feedback from an anonymous reviewer. JMS acknowledges NSF-DMR-1832002 and an Isaac Newton Award from the DoD. AEP acknowledges NIH R35 GM142963. JMS and AEP acknowledge a Syracuse University CUSE Grant and a Syracuse BioInspired Grant. SG acknowledges a graduate fellowship from Syracuse University.
Official Citation
Gupta S, Patteson AE, Schwarz JM. The role of vimentin-nuclear interactions in persistent cell motility through confined spaces. New J Phys. 2021 Sep;23:093042. doi: 10.1088/1367-2630/ac2550. Epub 2021 Sep 29. PMID: 35530563; PMCID: PMC9075336.
Disciplines
Physics
Description/Abstract
The ability of cells to move through small spaces depends on the mechanical properties of the cellular cytoskeleton and on nuclear deformability. In mammalian cells, the cytoskeleton is composed of three interacting, semi-flexible polymer networks: actin, microtubules, and intermediate filaments (IF). Recent experiments of mouse embryonic fibroblasts with and without vimentin have shown that the IF vimentin plays a role in confined cell motility. Here, we develop a minimal model of a cell moving through a microchannel that incorporates explicit effects of actin and vimentin and implicit effects of microtubules. Specifically, the model consists of a cell with an actomyosin cortex and a deformable cell nucleus and mechanical linkages between the two. By decreasing the amount of vimentin, we find that the cell speed increases for vimentin-null cells compared to cells with vimentin. The loss of vimentin increases nuclear deformation and alters nuclear positioning in the cell. Assuming nuclear positioning is a read-out for cell polarity, we propose a new polarity mechanism which couples cell directional motion with cytoskeletal strength and nuclear positioning and captures the abnormally persistent motion of vimentin-null cells, as observed in experiments. The enhanced persistence indicates that the vimentin-null cells are more controlled by the confinement and so less autonomous, relying more heavily on external cues than their wild-type counterparts. Our modeling results present a quantitative interpretation for recent experiments and have implications for understanding the role of vimentin in the epithelial–mesenchymal transition.
Recommended Citation
Gupta S, Patteson AE, Schwarz JM. The role of vimentin-nuclear interactions in persistent cell motility through confined spaces. New J Phys. 2021 Sep;23:093042. doi: 10.1088/1367-2630/ac2550. Epub 2021 Sep 29. PMID: 35530563; PMCID: PMC9075336.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
