A1 Refereed original research article in a scientific journal
Mechano-responsiveness of fibrillar adhesions on stiffness-gradient gels
Authors: Barber-Pérez N, Georgiadou M, Guzmán C, Isomursu A, Hamidi H, Ivaska J
Publisher: The Company of Biologists Ltd.
Publication year: 2020
Journal: Journal of Cell Science
Journal name in source: Journal of cell science
Journal acronym: J Cell Sci
Article number: jcs242909
Volume: 133
Issue: 12
Number of pages: 11
ISSN: 0021-9533
eISSN: 1477-9137
DOI: https://doi.org/10.1242/jcs.242909
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/48541903
Fibrillar adhesions are important structural and adhesive components in fibroblasts, and are required for fibronectin fibrillogenesis. While nascent and focal adhesions are known to respond to mechanical cues, the mechanoresponsive nature of fibrillar adhesions remains unclear. Here, we used ratiometric analysis of paired adhesion components to determine an appropriate fibrillar adhesion marker. We found that active α5β1-integrin exhibits the most definitive fibrillar adhesion localization compared to other proteins, such as tensin-1, reported to be in fibrillar adhesions. To elucidate the mechanoresponsiveness of fibrillar adhesions, we designed a cost-effective and reproducible technique to fabricate physiologically relevant stiffness gradients on thin polyacrylamide (PA) hydrogels, embedded with fluorescently labelled beads. We generated a correlation curve between bead density and hydrogel stiffness, thus enabling a readout of stiffness without the need for specialized knowhow, such as atomic force microscopy (AFM). We find that stiffness promotes growth of fibrillar adhesions in a tensin-1-dependent manner. Thus, the formation of these extracellular matrix-depositing structures is coupled to the mechanical parameters of the cell environment and may enable cells to fine-tune their matrix environment in response to changing physical conditions.
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