ORCID

Alison Patteson: 0000-0002-4004-1734

Minh Tri Ho Thanh: 0000-0002-9380-0191

Katherine Kerr: 0000-0003-1238-6564

Document Type

Article

Date

Winter 12-9-2022

Keywords

vimentin, cytoskeleton, extracellular matrix, cell adhesion, cell migration, glycocalyx

Language

English

Funder(s)

National Institutes of Health, Syracuse University SOURCE award, US National Science Foundation Center for Engineering Mechanobiology, and the National Science Center of Poland

Funding ID

NIH R35GM136259, NIH R35GM14296, CMMI-1548571, and UMO-2020/01/0/NZ6/ 00082

Acknowledgements

We thank Robert Goldman, John Eriksson, and Karen Ridge for materials and insightful discussions. We thank Bobby Carroll for assisting in vimentin preparations.

Official Citation

Bucki R, Iwamoto DV, Shi X, Kerr KE, Byfield FJ, Suprewicz Ł, Skłodowski K, Sutaria J, Misiak P, Wilczewska AZ, Ramachandran S, Wolfe A, Thanh MH, Whalen E, Patteson AE, Janmey PA. Extracellular vimentin is sufficient to promote cell attachment, spreading, and motility by a mechanism involving N-acetyl glucosamine-containing structures. J Biol Chem. 2023 Aug;299(8):104963. doi: 10.1016/j.jbc.2023.104963. Epub 2023 Jun 24. PMID: 37356720; PMCID: PMC10392088.

Disciplines

Physics

Description/Abstract

Vimentin intermediate !laments form part of the cytoskeleton

of mesenchymal cells, but under pathological conditions often

associatedwith in"ammation, vimentin !laments depolymerize as

the result of phosphorylation or citrullination, and vimentin

oligomers are secreted or released into the extracellular environment.

In the extracellular space, vimentin can bind surfaces of cells

and the extracellular matrix, and the interaction between extracellular

vimentin and cells can trigger changes in cellular functions,

such as activation of !broblasts to a !brotic phenotype. The

mechanism by which extracellular vimentin binds external cell

membranes and whether vimentin alone can act as an adhesive

anchor for cells is largely uncharacterized. Here, we show that

various cell types (normal and vimentin null !broblasts, mesenchymal

stem cells, and A549 lung carcinoma cells) attach to and

spread on polyacrylamide hydrogel substrates covalently linked to

vimentin. Using traction force microscopy and spheroid expansion

assays, we characterize how different cell types respond to

extracellular vimentin. Cell attachment to and spreading on

vimentin-coated surfaces is inhibited by hyaluronic acid degrading

enzymes, hyaluronic acid synthase inhibitors, soluble heparin

or N-acetyl glucosamine, all of which are treatments that have

little or no effect on the same cell types binding to collagen-coated

hydrogels. These studies highlight the effectiveness of substratebound

vimentin as a ligand for cells and suggest that carbohydrate

structures, including the glycocalyx and glycosylated cell

surface proteins that contain N-acetyl glucosamine, form a novel

class of adhesion receptors for extracellular vimentin that can

either directly support cell adhesion to a substrate or !ne-tune the

glycocalyx adhesive properties.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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