Cell shape-dependent early responses of fibroblasts to cyclic strain

Gadhari, Neha; Charnley, Mirren; Marelli, Mattia; Brugger, Jürgen; Chiquet, Matthias (2013). Cell shape-dependent early responses of fibroblasts to cyclic strain. Biochimica et biophysica acta - molecular cell research, 1833(12), pp. 3415-25. Elsevier 10.1016/j.bbamcr.2013.10.012

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Randomly spread fibroblasts on fibronectin-coated elastomeric membranes respond to cyclic strain by a varying degree of focal adhesion assembly and actin reorganization. We speculated that the individual shape of the cells, which is linked to cytoskeletal structure and pre-stress, might tune these integrin-dependent mechanotransduction events. To this aim, fibronectin circles, squares and rectangles of identical surface area (2000μm(2)) were micro-contact printed onto elastomeric substrates. Fibroblasts plated on these patterns occupied the corresponding shapes. Cyclic 10% equibiaxial strain was applied to patterned cells for 30min, and changes in cytoskeleton and cell-matrix adhesions were quantified after fluorescence staining. After strain, megakaryocytic leukemia-1 protein translocated to the nucleus in most cells, indicating efficient RhoA activation independently of cell shape. However, circular and square cells (with radial symmetry) showed a significantly greater increase in the number of actin stress fibers and vinculin-positive focal adhesions after cyclic strain than rectangular (bipolar) cells of identical size. Conversely, cyclic strain induced larger changes in pY397-FAK positive focal complexes and zyxin relocation from focal adhesions to stress fibers in bipolar compared to symmetric cells. Thus, radially symmetric cells responded to cyclic strain with a larger increase in assembly, whereas bipolar cells reacted with more pronounced reorganization of actin stress fibers and matrix contacts. We conclude that integrin-mediated responses to external mechanical strain are differentially modulated in cells that have the same spreading area but different geometries, and do not only depend on mere cell size.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > School of Dental Medicine > Department of Orthodontics

UniBE Contributor:

Gadhari, Neha and Chiquet, Matthias


600 Technology > 610 Medicine & health








Eveline Carmen Schuler

Date Deposited:

24 Jan 2014 12:04

Last Modified:

25 Jan 2017 12:15

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

4′,6-diamidino-2-phenylindole, Actin cytoskeleton, BSA, Bovine Serum Albumin, Cell shape, Cyclic strain, DAPI, DMEM, Dulbecco's Modified Eagle's Medium, ECM, FAK, FCS, Focal adhesion, HMDS, LIM, MEFs, MKL-1, Micro-contact printing, PBS, PDMS, ROCK, Ras homolog gene family, member A, Rho-associated Protein Kinase, RhoA, SRF, TRITC, extracellular matrix, fetal calf serum, focal adhesion kinase, hexamethyldisiloxane, lin-11, Isl-1 and mec-3, megakaryocytic leukemia-1, mouse embryonic fibroblasts, phosphate-buffered saline, polydimethylsiloxane, serum response factor, tetramethylrhodamine isothiocyanate





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