ArticleProceedings of the National Academy of Sciences of the United States of America2013
Orientation-specific responses to sustained uniaxial stretching in focal adhesion growth and turnover.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 98 citations in OpenAlex.
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- Sustained Strain Applied at High Rates Drives Dynamic Tensioning in Epithelial Cells.bioRxiv : the preprint server for biology · 2025Article
- Mechanical signaling regulates vascular smooth muscle cell adaptation in aging.Frontiers in physiology · 2025Article
- Focal adhesions are controlled by microtubules through local contractility regulation.The EMBO journal · 2024Article
- Biomechanical Aspects in Bone Tumor Engineering.Tissue engineering. Part B, Reviews · 2024Review
- Extracellular Matrix Cues Regulate Mechanosensing and Mechanotransduction of Cancer Cells.Cells · 2024Review
- From stress fiber to focal adhesion: a role of actin crosslinkers in force transmission.Frontiers in cell and developmental biology · 2024Review
- Increasing pulse pressure ex vivo, mimicking acute physical exercise, induces smooth muscle cell-mediated de-stiffening of murine aortic segments.Communications biology · 2023Article
- Understanding the driving force for cell migration plasticity.Biophysical journal · 2023Review
- Engineering tools for quantifying and manipulating forces in epithelia.Biophysics reviews · 2023Review
- Smooth Muscle-Alpha Actin R149C Pathogenic Variant Downregulates Integrin Recruitment at Cell-Matrix Adhesions and Decreases Cellular Contractility.International journal of molecular sciences · 2023Article
- A Statistical Mechanics Approach to Describe Cell Reorientation Under Stretch.Bulletin of mathematical biology · 2023Article
- Cyclic Stretch-Induced Mechanical Stress Applied at 1 Hz Frequency Can Alter the Metastatic Potential Properties of SAOS-2 Osteosarcoma Cells.International journal of molecular sciences · 2023Article
- Organization, dynamics and mechanoregulation of integrin-mediated cell-ECM adhesions.Nature reviews. Molecular cell biology · 2023Review
- Vinculin transmits high-level integrin tensions that are dispensable for focal adhesion formation.Biophysical journal · 2023Article
- High GNG4 predicts adverse prognosis for osteosarcoma: Bioinformatics prediction and experimental verification.Frontiers in oncology · 2023Article
- Membrane Ruffling is a Mechanosensor of Extracellular Fluid Viscosity.Nature physics · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cells are mechanosensitive to extracellular matrix (ECM) deformation, which can be caused by muscle contraction or changes in hydrostatic pressure. Focal adhesions (FAs) mediate the linkage between the cell and the ECM and initiate mechanically stimulated signaling events. We developed a stretching apparatus in which cells grown on fibronectin-coated elastic substrates can be stretched and imaged live to study how FAs dynamically respond to ECM deformation. Human bone osteosarcoma epithelial cell line U2OS was transfected with GFP-paxillin as an FA marker and subjected to sustained uniaxial stretching. Two responses at different timescales were observed: rapid FA growth within seconds after stretching, and delayed FA disassembly and loss of cell polarity that occurred over tens of minutes. Rapid FA growth occurred in all cells; however, delayed responses to stretch occurred in an orientation-specific manner, specifically in cells with their long axes perpendicular to the stretching direction, but not in cells with their long axes parallel to stretch. Pharmacological treatments demonstrated that FA kinase (FAK) promotes but Src inhibits rapid FA growth, whereas FAK, Src, and calpain 2 all contribute to delayed FA disassembly and loss of polarity in cells perpendicular to stretching. Immunostaining for phospho-FAK after stretching revealed that FAK activation was maximal at 5 s after stretching, specifically in FAs oriented perpendicular to stretch. We hypothesize that orientation-specific activation of strain/stress-sensitive proteins in FAs upstream to FAK and Src promote orientation-specific responses in FA growth and disassembly that mediate polarity rearrangement in response to sustained stretch.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.