| Absence of filamin A prevents cells from responding to stiffness gradients on gels coated with collagen but not fibronectin. | |
| | |
MedLine Citation:
|
PMID: 19527669 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Cell types from many tissues respond to changes in substrate stiffness by actively remodeling their cytoskeletons to alter spread area or adhesion strength, and in some cases changing their own stiffness to match that of their substrate. These cell responses to substrate stiffness are linked to substrate-induced changes in the state, localization, and amount of numerous proteins, but detailed evidence for the requirement of specific proteins in these distinct forms of mechanical response are scarce. Here we use microfluidics techniques to produce gels with a gradient of stiffness to show the essential function of filamin A in cell responses to mechanical stimuli and dissociate cell spreading and stiffening by contrasting responses of a pair of human melanoma-derived cell lines that differ in expression of this actin cross-linking protein. M2 melanoma cells null for filamin A do not alter their adherent area in response to increased substrate stiffness when they link to the substrate only through collagen receptors, but change adherent area normally when bound through fibronectin receptors. In contrast, filamin A-replete A7 cells change adherent area on both substrates and respond more strongly to collagen I-coated gels than to fibronectin-coated gels. Strikingly, A7 cells alter their stiffness, as measured by atomic force microscopy, to match the elastic modulus of the substrate immediately adjacent to them on the gradient. M2 cells, in contrast, maintain a constant stiffness on all substrates that is as low as that of A7 cells on the softest gels examined (1000 Pa). Comparison of cell spreading and cell stiffening on the same gradient substrates shows that cell spreading is uncoupled from stiffening. At saturating collagen and fibronectin concentrations, adhesion of M2 cells is reduced compared to that of A7 cells to an extent approximately equal to the difference in adherent area. Filamin A appears to be essential for cell stiffening on collagen, but not for cell spreading on fibronectin. These results have implications for different models of cell protrusion and adhesion and identify a key role for filamin A in altering cellular stiffness that cannot be compensated for by other actin cross-linkers in vivo. |
| | |
Authors:
|
Fitzroy J Byfield; Qi Wen; Ilya Levental; Kerstin Nordstrom; Paulo E Arratia; R Tyler Miller; Paul A Janmey |
Related Documents
:
|
20006339 - Cells in 3d matrices under interstitial flow: effects of extracellular matrix alignment... 16250009 - Hydrodynamic compression of young and adult rat osteoblast-like cells on titanium fiber... 19325879 - Assembly and development of the pseudomonas aeruginosa biofilm matrix. 15827669 - Mesenchymal stem cells in musculoskeletal tissue engineering: a review of recent advanc... 6540429 - Trabecular meshwork cell culture in glaucoma research: evaluation of biological activit... 17177849 - Investigating the effects of preinduction on human adipose-derived precursor cells in a... 8100859 - The neuroendocrine cell population of the human prostate gland. 16415209 - The epidermis-specific extracellular bodyguard controls cuticle development and morphog... 16598689 - The schizosaccharomyces pombe cfr1+ gene participates in mating through a new pathway t... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
|
Title: Biophysical journal Volume: 96 ISSN: 1542-0086 ISO Abbreviation: Biophys. J. Publication Date: 2009 Jun |
Date Detail:
|
Created Date: 2009-06-16 Completed Date: 2009-08-25 Revised Date: 2010-09-27 |
Medline Journal Info:
|
Nlm Unique ID: 0370626 Medline TA: Biophys J Country: United States |
Other Details:
|
Languages: eng Pagination: 5095-102 Citation Subset: IM |
Affiliation:
|
Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Adhesion Cell Line Collagen / metabolism* Contractile Proteins / metabolism* Fibronectins / metabolism Gels Melanoma / metabolism Microfilament Proteins / metabolism* Microscopy, Atomic Force Substrate Specificity |
| Grant Support | |
ID/Acronym/Agency:
|
GM083272/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Contractile Proteins; 0/Fibronectins; 0/Gels; 0/Microfilament Proteins; 0/filamins; 9007-34-5/Collagen |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Improved model of fluorescence recovery expands the application of multiphoton fluorescence recovery...
Next Document: A novel approach to high accuracy of video-based microrheology.