{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T05:29:45Z","timestamp":1773466185999,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T00:00:00Z","timestamp":1479168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T00:00:00Z","timestamp":1479168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Integrins coupled with other proteins form protein complexes named focal adhesions (FA) which are considered as the primary sites for cellular forces transduction during cell stable adhesion. Cell traction forces transmitted by FAs and integrin tensions inside FAs have been extensively studied. However, it remains unknown whether integrins outside FAs can transmit tension, and if so, what is the tension range. We previously developed a tension sensor named tension gauge tether (TGT). To calibrate integrin tensions outside FAs, here we applied multiplex TGT (mTGT) to simultaneously monitor integrin tensions at separate levels. mTGT unambiguously revealed that integrins outside FAs also transmit tension after FA formation. These tensions are mainly located in the range of 43\u2009~\u200954 pN which is lower than integrin tensions inside FAs. Integrin tensions both inside and outside FAs substantially contribute to bulk cellular forces and they respond independently to actin and myosin II inhibition, serum deprivation and microtubule inhibition, indicating their different tension sources and independent dynamics. Our work identified integrin tensions outside FAs and calibrated the tension range for the first time. We also demonstrated that mTGT is a valuable tool to monitor integrin tension profile in a broad detection range of 10\u2009~\u200960 pN.<\/jats:p>","DOI":"10.1038\/srep36959","type":"journal-article","created":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T11:26:23Z","timestamp":1479209183000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Integrins outside focal adhesions transmit tensions during stable cell adhesion"],"prefix":"10.1038","volume":"6","author":[{"given":"Yongliang","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,11,15]]},"reference":[{"key":"BFsrep36959_CR1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/0092-8674(92)90115-S","volume":"69","author":"RO Hynes","year":"1992","unstructured":"Hynes, R. O. Integrins - Versatility, Modulation, and Signaling in Cell-Adhesion. Cell 69, 11\u201325 (1992).","journal-title":"Cell"},{"key":"BFsrep36959_CR2","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1126\/science.1091325","volume":"303","author":"AF Palazzo","year":"2004","unstructured":"Palazzo, A. F., Eng, C. H., Schlaepfer, D. D., Marcantonio, E. E. & Gundersen, G. G. Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling. Science 303, 836\u2013839 (2004).","journal-title":"Science"},{"key":"BFsrep36959_CR3","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/0092-8674(87)90009-2","volume":"51","author":"AS Menko","year":"1987","unstructured":"Menko, A. S. & Boettiger, D. Occupation of the Extracellular-Matrix Receptor, Integrin, Is a Control Point for Myogenic Differentiation. Cell 51, 51\u201357 (1987).","journal-title":"Cell"},{"key":"BFsrep36959_CR4","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/S0955-0674(98)80145-2","volume":"10","author":"ME Chicurel","year":"1998","unstructured":"Chicurel, M. E., Chen, C. S. & Ingber, D. E. Cellular control lies in the balance of forces. Curr Opin Cell Biol 10, 232\u2013239 (1998).","journal-title":"Curr Opin Cell Biol"},{"key":"BFsrep36959_CR5","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/35074532","volume":"3","author":"NQ Balaban","year":"2001","unstructured":"Balaban, N. Q. et al. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat Cell Biol 3, 466\u2013472 (2001).","journal-title":"Nat Cell Biol"},{"key":"BFsrep36959_CR6","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/nrm2593","volume":"10","author":"B Geiger","year":"2009","unstructured":"Geiger, B., Spatz, J. P. & Bershadsky, A. D. Environmental sensing through focal adhesions. Nat Rev Mol Cell Bio 10, 21\u201333 (2009).","journal-title":"Nat Rev Mol Cell Bio"},{"key":"BFsrep36959_CR7","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1126\/science.6987736","volume":"208","author":"AK Harris","year":"1980","unstructured":"Harris, A. K., Wild, P. & Stopak, D. Silicone rubber substrata: a new wrinkle in the study of cell locomotion. Science 208, 177\u2013179 (1980).","journal-title":"Science"},{"key":"BFsrep36959_CR8","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/nmeth.1531","volume":"7","author":"WR Legant","year":"2010","unstructured":"Legant, W. R. et al. Measurement of mechanical tractions exerted by cells in three-dimensional matrices. Nat Methods 7, 969\u2013U113 (2010).","journal-title":"Nat Methods"},{"key":"BFsrep36959_CR9","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1529\/biophysj.107.113670","volume":"94","author":"B Sabass","year":"2008","unstructured":"Sabass, B., Gardel, M. L., Waterman, C. M. & Schwarz, U. S. High resolution traction force microscopy based on experimental and computational advances. Biophys J 94, 207\u2013220 (2008).","journal-title":"Biophys J"},{"key":"BFsrep36959_CR10","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/nature09621","volume":"468","author":"P Kanchanawong","year":"2010","unstructured":"Kanchanawong, P. et al. Nanoscale architecture of integrin-based cell adhesions. Nature 468, 580\u2013U262 (2010).","journal-title":"Nature"},{"key":"BFsrep36959_CR11","doi-asserted-by":"publisher","first-page":"4329","DOI":"10.1091\/mbc.e05-02-0170","volume":"16","author":"ND Gallant","year":"2005","unstructured":"Gallant, N. D., Michael, K. E. & Garcia, A. J. Cell adhesion strengthening: Contributions of adhesive area, integrin binding, and focal adhesion assembly. Mol Biol Cell 16, 4329\u20134340 (2005).","journal-title":"Mol Biol Cell"},{"key":"BFsrep36959_CR12","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1146\/annurev.cellbio.19.111301.153011","volume":"19","author":"AD Bershadsky","year":"2003","unstructured":"Bershadsky, A. D., Balaban, N. Q. & Geiger, B. Adhesion-dependent cell mechanosensitivity. Annual Review of Cell and Developmental Biology 19, 677\u2013695 (2003).","journal-title":"Annual Review of Cell and Developmental Biology"},{"key":"BFsrep36959_CR13","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nature09198","volume":"466","author":"C Grashoff","year":"2010","unstructured":"Grashoff, C. et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466, 263\u2013U143 (2010).","journal-title":"Nature"},{"key":"BFsrep36959_CR14","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/nmeth.1747","volume":"9","author":"DR Stabley","year":"2012","unstructured":"Stabley, D. R., Jurchenko, C., Marshall, S. S. & Salaita, K. S. Visualizing mechanical tension across membrane receptors with a fluorescent sensor. Nat Methods 9, 64\u2013U172 (2012).","journal-title":"Nat Methods"},{"key":"BFsrep36959_CR15","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1021\/nl4005145","volume":"13","author":"M Morimatsu","year":"2013","unstructured":"Morimatsu, M., Mekhdjian, A. H., Adhikari, A. S. & Dunn, A. R. Molecular Tension Sensors Report Forces Generated by Single Integrin Molecules in Living Cells. Nano Lett 13, 3985\u20133989 (2013).","journal-title":"Nano Lett"},{"key":"BFsrep36959_CR16","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1038\/nmeth.3145","volume":"11","author":"BL Blakely","year":"2014","unstructured":"Blakely, B. L. et al. A DNA-based molecular probe for optically reporting cellular traction forces. Nat Methods 11, 1229\u20131232 (2014).","journal-title":"Nat Methods"},{"key":"BFsrep36959_CR17","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Ge, C. H., Zhu, C. & Salaita, K. DNA-based digital tension probes reveal integrin forces during early cell adhesion. Nat Commun 5 (2014).","DOI":"10.1038\/ncomms6167"},{"key":"BFsrep36959_CR18","doi-asserted-by":"publisher","first-page":"2901","DOI":"10.1021\/jacs.5b11602","volume":"138","author":"Y Chang","year":"2016","unstructured":"Chang, Y. et al. A General Approach for Generating Fluorescent Probes to Visualize Piconewton Forces at the Cell Surface. J Am Chem Soc 138, 2901\u20132904 (2016).","journal-title":"J Am Chem Soc"},{"key":"BFsrep36959_CR19","doi-asserted-by":"publisher","first-page":"5539","DOI":"10.1021\/nl501912g","volume":"14","author":"Y Liu","year":"2014","unstructured":"Liu, Y. et al. Nanoparticle Tension Probes Patterned at the Nanoscale: Impact of Integrin Clustering on Force Transmission. Nano Lett 14, 5539\u20135546 (2014).","journal-title":"Nano Lett"},{"key":"BFsrep36959_CR20","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1016\/j.bpj.2015.10.029","volume":"109","author":"XF Wang","year":"2015","unstructured":"Wang, X. F. et al. Integrin Molecular Tension within Motile Focal Adhesions. Biophys J 109, 2259\u20132267 (2015).","journal-title":"Biophys J"},{"key":"BFsrep36959_CR21","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1021\/acs.nanolett.5b03888","volume":"16","author":"K Galior","year":"2016","unstructured":"Galior, K., Liu, Y., Yehl, K., Vivek, S. & Salaita, K. Titin-Based Nanoparticle Tension Sensors Map High-Magnitude Integrin Forces within Focal Adhesions. Nano Lett 16, 341\u2013348 (2016).","journal-title":"Nano Lett"},{"key":"BFsrep36959_CR22","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1126\/science.1231041","volume":"340","author":"XF Wang","year":"2013","unstructured":"Wang, X. F. & Ha, T. Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling. Science 340, 991\u2013994 (2013).","journal-title":"Science"},{"key":"BFsrep36959_CR23","doi-asserted-by":"crossref","unstructured":"Hatch, K., Danilowicz, C., Coljee, V. & Prentiss, M. Demonstration that the shear force required to separate short double-stranded DNA does not increase significantly with sequence length for sequences longer than 25 base pairs. Phys Rev E 78 (2008).","DOI":"10.1103\/PhysRevE.78.011920"},{"key":"BFsrep36959_CR24","doi-asserted-by":"publisher","first-page":"8608","DOI":"10.1073\/pnas.151257598","volume":"98","author":"S Cocco","year":"2001","unstructured":"Cocco, S., Monasson, R. & Marko, J. F. Force and kinetic barriers to unzipping of the DNA double helix. P Natl Acad Sci USA 98, 8608\u20138613 (2001).","journal-title":"P Natl Acad Sci USA"},{"key":"BFsrep36959_CR25","doi-asserted-by":"publisher","first-page":"7461","DOI":"10.1021\/ja9603721","volume":"118","author":"R Haubner","year":"1996","unstructured":"Haubner, R. et al. Structural and functional aspects of RGD-containing cyclic pentapeptides as highly potent and selective integrin alpha (v) beta (3) antagonists. J Am Chem Soc 118, 7461\u20137472 (1996).","journal-title":"J Am Chem Soc"},{"key":"BFsrep36959_CR26","doi-asserted-by":"publisher","first-page":"6249","DOI":"10.1016\/j.biomaterials.2013.04.065","volume":"34","author":"G Mondal","year":"2013","unstructured":"Mondal, G., Barui, S. & Chaudhuri, A. The relationship between the cyclic-RGDfK ligand and alpha v beta 3 integrin receptor. Biomaterials 34, 6249\u20136260 (2013).","journal-title":"Biomaterials"},{"key":"BFsrep36959_CR27","doi-asserted-by":"publisher","first-page":"11993","DOI":"10.1021\/acsnano.5b04726","volume":"9","author":"M Mosayebi","year":"2015","unstructured":"Mosayebi, M., Louis, A. A., Doye, J. P. K. & Ouldridge, T. E. Force-Induced Rupture of a DNA Duplex: From Fundamentals to Force Sensors. Acs Nano 9, 11993\u201312003 (2015).","journal-title":"Acs Nano"},{"key":"BFsrep36959_CR28","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/nrm2957","volume":"11","author":"JT Parsons","year":"2010","unstructured":"Parsons, J. T., Horwitz, A. R. & Schwartz, M. A. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Bio 11, 633\u2013643 (2010).","journal-title":"Nat Rev Mol Cell Bio"},{"key":"BFsrep36959_CR29","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1146\/annurev-cellbio-101011-155711","volume":"29","author":"S Etienne-Manneville","year":"2013","unstructured":"Etienne-Manneville, S. Microtubules in Cell Migration. Annu Rev Cell Dev Bi 29, 471\u2013499 (2013).","journal-title":"Annu Rev Cell Dev Bi"},{"key":"BFsrep36959_CR30","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/35024000","volume":"407","author":"DJ Sharp","year":"2000","unstructured":"Sharp, D. J., Rogers, G. C. & Scholey, J. M. Microtubule motors in mitosis. Nature 407, 41\u201347 (2000).","journal-title":"Nature"},{"key":"BFsrep36959_CR31","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/ncb1262","volume":"7","author":"EJ Ezratty","year":"2005","unstructured":"Ezratty, E. J., Partridge, M. A. & Gundersen, G. G. Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol 7, 581\u2013U515 (2005).","journal-title":"Nat Cell Biol"},{"key":"BFsrep36959_CR32","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1091\/mbc.8.6.973","volume":"8","author":"RJ Vasquez","year":"1997","unstructured":"Vasquez, R. J., Howell, B., Yvon, A. M. C., Wadsworth, P. & Cassimeris, L. Nanomolar concentrations of nocodazole alter microtubule dynamic instability in vivo and in vitro . Mol Biol Cell 8, 973\u2013985 (1997).","journal-title":"Mol Biol Cell"},{"key":"BFsrep36959_CR33","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0022-3565(25)31589-2","volume":"208","author":"F Samson","year":"1979","unstructured":"Samson, F., Donoso, J. A., Hellerbettinger, I., Watson, D. & Himes, R. H. Nocodazole Action on Tubulin Assembly, Axonal Ultrastructure and Fast Axoplasmic-Transport. J Pharmacol Exp Ther 208, 411\u2013417 (1979).","journal-title":"J Pharmacol Exp Ther"},{"key":"BFsrep36959_CR34","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1101\/gad.1511207","volume":"21","author":"SE Siegrist","year":"2007","unstructured":"Siegrist, S. E. & Doe, C. Q. Microtubule-induced cortical cell polarity. Gene Dev 21, 483\u2013496 (2007).","journal-title":"Gene Dev"},{"key":"BFsrep36959_CR35","doi-asserted-by":"crossref","unstructured":"Taherian, A., Li, X. L., Liu, Y. Q. & Haas, T. A. Differences in integrin expression and signaling within human breast cancer cells. Bmc Cancer 11 (2011).","DOI":"10.1186\/1471-2407-11-293"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep36959.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36959","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36959.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T15:41:49Z","timestamp":1749742909000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep36959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,15]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep36959"],"URL":"https:\/\/doi.org\/10.1038\/srep36959","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,15]]},"assertion":[{"value":"8 July 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36959"}}