ORCID
Alison E. Patteson: 0000-0002-4004-1734
Document Type
Article
Date
Fall 11-13-2019
Language
English
Funder(s)
National Institutes of Health-National Institute of General Medical Sciences, U.S. National Science Foundation, the National Science Center, Poland under Grant,
Funding ID
P01 GM096971, CMMI-154857 and DMR-1720530, UMO-2015/17/B/NZ6/03473, UMO-2016/26/D/ST4/00997,
Acknowledgements
This work was supported by the National Institutes of Health-National Institute of General Medical Sciences (P01 GM096971), the U.S. National Science Foundation (CMMI-154857 and DMR-1720530), and the National Science Center, Poland under Grant No. UMO-2015/17/B/NZ6/03473 (to RB) and UMO-2016/26/D/ST4/00997 (to KP). The authors thank Dennis Discher and Manu Tewari for help amplifying the pEGF-C1-NLS plasmid. The authors also thank Eric Johnston and Nathan Bade for help developing the microfluidic device and Mateusz Cieśluk for his technical assistance during AFM experiments. The authors kindly thank Arvind Gopinath, Ravi Radhakrishnan, and Jennifer Schwarz for insight and feedback on the motility model. A.E.P. designed, performed, and analyzed motility experiments using microfluidics devices and Transwell membrane assays. F.B. designed and performed capillary experiments and analysis. K.P., R.B., and P.D. designed and performed AFM measurements and analysis. K.M. performed and analyzed TFM measurements. E.C. and P.G. developed microfluidic device. Z.O. and C.M. performed Western blot detection of phospho-myosin. A.E.P., F.B., K.P., E.C., P.G., and P.A.J. contributed to project design and wrote the manuscript.
Official Citation
Patteson AE, Pogoda K, Byfield FJ, Mandal K, Ostrowska-Podhorodecka Z, Charrier EE, Galie PA, Deptuła P, Bucki R, McCulloch CA, Janmey PA. Loss of Vimentin Enhances Cell Motility through Small Confining Spaces. Small. 2019 Dec;15(50):e1903180. doi: 10.1002/smll.201903180. Epub 2019 Nov 13. PMID: 31721440; PMCID: PMC6910987.
Disciplines
Physics
Description/Abstract
The migration of cells through constricting spaces or along fibrous tracks in tissues is important for many biological processes and depends on the mechanical properties of a cytoskeleton made up of three different filaments: F-actin, microtubules, and intermediate filaments. The signaling pathways and cytoskeletal structures that control cell motility on 2D are often very different from those that control motility in 3D. Previous studies have shown that intermediate filaments can promote actin-driven protrusions at the cell edge, but have little effect on overall motility of cells on flat surfaces. They are however important for cells to maintain resistance to repeated compressive stresses that are expected to occur in vivo. Using mouse embryonic fibroblasts derived from wild-type and vimentin-null mice, it is found that loss of vimentin increases motility in 3D microchannels even though on flat surfaces it has the opposite effect. Atomic force microscopy and traction force microscopy experiments reveal that vimentin enhances perinuclear cell stiffness while maintaining the same level of acto-myosin contractility in cells. A minimal model in which a perinuclear vimentin cage constricts along with the nucleus during motility through confining spaces, providing mechanical resistance against large strains that could damage the structural integrity of cells, is proposed.
Recommended Citation
Patteson AE, Pogoda K, Byfield FJ, Mandal K, Ostrowska-Podhorodecka Z, Charrier EE, Galie PA, Deptuła P, Bucki R, McCulloch CA, Janmey PA. Loss of Vimentin Enhances Cell Motility through Small Confining Spaces. Small. 2019 Dec;15(50):e1903180. doi: 10.1002/smll.201903180. Epub 2019 Nov 13. PMID: 31721440; PMCID: PMC6910987.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
