{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:32:03Z","timestamp":1775889123241,"version":"3.50.1"},"reference-count":99,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:00:00Z","timestamp":1536883200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Protoc"],"published-print":{"date-parts":[[2018,10]]},"DOI":"10.1038\/s41596-018-0031-8","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T15:57:24Z","timestamp":1536940644000},"page":"2200-2216","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Mapping heterogeneity of cellular mechanics by multi-harmonic atomic force microscopy"],"prefix":"10.1038","volume":"13","author":[{"given":"Yuri M.","family":"Efremov","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6227-2499","authenticated-orcid":false,"given":"Alexander X.","family":"Cartagena-Rivera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad I. M.","family":"Athamneh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel M.","family":"Suter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arvind","family":"Raman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,9,14]]},"reference":[{"key":"31_CR1","doi-asserted-by":"publisher","first-page":"11594","DOI":"10.1073\/pnas.0502575102","volume":"102","author":"CM Nelson","year":"2005","unstructured":"Nelson, C. M. et al. Emergent patterns of growth controlled by multicellular form and mechanics. Proc. Natl. Acad. Sci. USA 102, 11594\u201311599 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"31_CR2","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nrm2594","volume":"10","author":"N Wang","year":"2009","unstructured":"Wang, N., Tytell, J. D. & Ingber, D. E. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat. Rev. Mol. Cell Biol. 10, 75\u201382 (2009).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"31_CR3","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1073\/pnas.96.3.921","volume":"96","author":"C Rotsch","year":"1999","unstructured":"Rotsch, C., Jacobson, K. & Radmacher, M. Dimensional and mechanical dynamics of active and stable edges in motile fibroblasts investigated by using atomic force microscopy. Proc. Natl. Acad. Sci. USA 96, 921\u2013926 (1999).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"31_CR4","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.1016\/j.yexcr.2013.04.023","volume":"319","author":"JR Lange","year":"2013","unstructured":"Lange, J. R. & Fabry, B. Cell and tissue mechanics in cell migration. Exp. Cell Res. 319, 2418\u20132423 (2013).","journal-title":"Exp. Cell Res."},{"key":"31_CR5","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.ceb.2010.10.015","volume":"23","author":"P Friedl","year":"2011","unstructured":"Friedl, P., Wolf, K. & Lammerding, J. Nuclear mechanics during cell migration. Curr. Opin. Cell Biol. 23, 55\u201364 (2011).","journal-title":"Curr. Opin. Cell Biol."},{"key":"31_CR6","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1146\/annurev-bioeng-071811-150045","volume":"15","author":"K Franze","year":"2013","unstructured":"Franze, K., Janmey, P. A. & Guck, J. Mechanics in neuronal development and repair. Annu. Rev. Biomed. Eng. 15, 227\u2013251 (2013).","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"31_CR7","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s10555-008-9173-4","volume":"28","author":"S Kumar","year":"2009","unstructured":"Kumar, S. & Weaver, V. M. Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev. 28, 113\u2013127 (2009).","journal-title":"Cancer Metastasis Rev."},{"key":"31_CR8","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nrc3080","volume":"11","author":"D Wirtz","year":"2011","unstructured":"Wirtz, D., Konstantopoulos, K. & Searson, P. C. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer 11, 512\u2013522 (2011).","journal-title":"Nat. Rev. Cancer"},{"key":"31_CR9","doi-asserted-by":"publisher","first-page":"3989","DOI":"10.1016\/j.actamat.2007.04.022","volume":"55","author":"S Suresh","year":"2007","unstructured":"Suresh, S. Biomechanics and biophysics of cancer cells. Acta Mater. 55, 3989\u20134014 (2007).","journal-title":"Acta Mater."},{"key":"31_CR10","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/S0006-3495(00)76614-8","volume":"78","author":"C Rotsch","year":"2000","unstructured":"Rotsch, C. & Radmacher, M. Drug-induced changes of cytoskeletal structure and mechanics in fibroblasts: an atomic force microscopy study. Biophys. J. 78, 520\u2013535 (2000).","journal-title":"Biophys. J."},{"key":"31_CR11","doi-asserted-by":"publisher","first-page":"3117","DOI":"10.1016\/j.bbamcr.2015.05.008","volume":"1853","author":"YM Efremov","year":"2015","unstructured":"Efremov, Y. M. et al. Distinct impact of targeted actin cytoskeleton reorganization on mechanical properties of normal and malignant cells. Biochim. Biophys. Acta 1853, 3117\u20133125 (2015).","journal-title":"Biochim. Biophys. Acta"},{"key":"31_CR12","unstructured":"Grady, M. E., Composto, R. J. & Eckmann, D. M. in Mechanics of Biological Systems and Materials (eds. Barthelat, F., Zavattieri, P., Korach, C. S., Prorok, B. C. & Grande-Allen, K. J.) 6, 169\u2013177 (Springer, New York, 2017)."},{"key":"31_CR13","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/nnano.2007.388","volume":"2","author":"SE Cross","year":"2007","unstructured":"Cross, S. E., Jin, Y. S., Rao, J. & Gimzewski, J. K. Nanomechanical analysis of cells from cancer patients. Nat. Nanotechnol. 2, 780\u2013783 (2007).","journal-title":"Nat. Nanotechnol."},{"key":"31_CR14","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1016\/j.micron.2012.01.019","volume":"43","author":"M Lekka","year":"2012","unstructured":"Lekka, M. et al. Cancer cell recognition\u2013mechanical phenotype. Micron 43, 1259\u20131266 (2012).","journal-title":"Micron"},{"key":"31_CR15","doi-asserted-by":"publisher","first-page":"393","DOI":"10.2217\/nnm.12.215","volume":"9","author":"RW Zwieten van","year":"2014","unstructured":"van Zwieten, R. W. et al. Assessing dystrophies and other muscle diseases at the nanometer scale by atomic force microscopy. Nanomedicine 9, 393\u2013406 (2014).","journal-title":"Nanomedicine"},{"key":"31_CR16","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.yexcr.2015.10.029","volume":"343","author":"K Burridge","year":"2016","unstructured":"Burridge, K. & Guilluy, C. Focal adhesions, stress fibers and mechanical tension. Exp. Cell Res. 343, 14\u201320 (2016).","journal-title":"Exp. Cell Res."},{"key":"31_CR17","doi-asserted-by":"publisher","first-page":"046603","DOI":"10.1088\/0034-4885\/77\/4\/046603","volume":"77","author":"DE Ingber","year":"2014","unstructured":"Ingber, D. E., Wang, N. & Stamenovic, D. Tensegrity, cellular biophysics, and the mechanics of living systems. Rep. Prog. Phys. 77, 046603 (2014).","journal-title":"Rep. Prog. Phys."},{"key":"31_CR18","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/j.cell.2012.11.034","volume":"151","author":"SV Plotnikov","year":"2012","unstructured":"Plotnikov, S. V., Pasapera, A. M., Sabass, B. & Waterman, C. M. Force fluctuations within focal adhesions mediate ECM-rigidity sensing to guide directed cell migration. Cell 151, 1513\u20131527 (2012).","journal-title":"Cell"},{"key":"31_CR19","doi-asserted-by":"publisher","first-page":"C1245","DOI":"10.1152\/ajpcell.00417.2009","volume":"298","author":"CY Park","year":"2010","unstructured":"Park, C. Y. et al. Mapping the cytoskeletal prestress. Am. J. Physiol. Cell Physiol. 298, C1245\u2013C1252 (2010).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"31_CR20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S0021-9290(99)00175-X","volume":"33","author":"RM Hochmuth","year":"2000","unstructured":"Hochmuth, R. M. Micropipette aspiration of living cells. J. Biomech. 33, 15\u201322 (2000).","journal-title":"J. Biomech."},{"key":"31_CR21","doi-asserted-by":"publisher","first-page":"2224","DOI":"10.1529\/biophysj.104.050278","volume":"88","author":"N Desprat","year":"2005","unstructured":"Desprat, N., Richert, A., Simeon, J. & Asnacios, A. Creep function of a single living cell. Biophys. J. 88, 2224\u20132233 (2005).","journal-title":"Biophys. J."},{"key":"31_CR22","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0021-9290(01)00201-9","volume":"35","author":"N Caille","year":"2002","unstructured":"Caille, N., Thoumine, O., Tardy, Y. & Meister, J. J. Contribution of the nucleus to the mechanical properties of endothelial cells. J. Biomech. 35, 177\u2013187 (2002).","journal-title":"J. Biomech."},{"key":"31_CR23","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13628-016-0031-4","volume":"9","author":"YA Ayala","year":"2016","unstructured":"Ayala, Y. A. et al. Rheological properties of cells measured by optical tweezers. BMC Biophys. 9, 5 (2016).","journal-title":"BMC Biophys."},{"key":"31_CR24","doi-asserted-by":"publisher","first-page":"8594","DOI":"10.1364\/OE.16.008594","volume":"16","author":"MT Wei","year":"2008","unstructured":"Wei, M.-T. et al. A comparative study of living cell micromechanical properties by oscillatory optical tweezers. Opt. Express 16, 8594\u20138603 (2008).","journal-title":"Opt. Express"},{"key":"31_CR25","doi-asserted-by":"publisher","first-page":"C1184","DOI":"10.1152\/ajpcell.00224.2004","volume":"287","author":"S Hu","year":"2004","unstructured":"Hu, S. et al. Mechanical anisotropy of adherent cells probed by a three-dimensional magnetic twisting device. Am. J. Physiol. Cell Physiol. 287, C1184\u2013C1191 (2004).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"31_CR26","doi-asserted-by":"publisher","first-page":"10259","DOI":"10.1073\/pnas.0510348103","volume":"103","author":"BD Hoffman","year":"2006","unstructured":"Hoffman, B. D., Massiera, G., Van Citters, K. M. & Crocker, J. C. The consensus mechanics of cultured mammalian cells. Proc. Natl. Acad. Sci. USA 103, 10259\u201310264 (2006).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"31_CR27","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S0304-3991(99)00157-6","volume":"82","author":"H Haga","year":"2000","unstructured":"Haga, H. et al. Elasticity mapping of living fibroblasts by AFM and immunofluorescence observation of the cytoskeleton. Ultramicroscopy 82, 253\u2013258 (2000).","journal-title":"Ultramicroscopy"},{"key":"31_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/srep11692","volume":"5","author":"AX Cartagena-Rivera","year":"2015","unstructured":"Cartagena-Rivera, A. X., Wang, W.-H., Geahlen, R. L. & Raman, A. Fast, multi-frequency, and quantitative nanomechanical mapping of live cells using the atomic force microscope. Sci. Rep. 5, 11692 (2015).","journal-title":"Sci. Rep."},{"key":"31_CR29","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1016\/S0006-3495(98)77868-3","volume":"74","author":"E A-Hassan","year":"1998","unstructured":"A-Hassan, E. et al. Relative microelastic mapping of living cells by atomic force microscopy. Biophys. J. 74, 1564\u20131578 (1998).","journal-title":"Biophys. J."},{"key":"31_CR30","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.micron.2007.06.011","volume":"38","author":"TG Kuznetsova","year":"2007","unstructured":"Kuznetsova, T. G., Starodubtseva, M. N., Yegorenkov, N. I., Chizhik, S. A. & Zhdanov, R. I. Atomic force microscopy probing of cell elasticity. Micron 38, 824\u2013833 (2007).","journal-title":"Micron"},{"key":"31_CR31","doi-asserted-by":"crossref","unstructured":"Gavara, N. A beginner\u2019s guide to atomic force microscopy probing for cell mechanics. Microsc. Res. Tech. 1\u201310 (2016).","DOI":"10.1002\/jemt.22776"},{"key":"31_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01784-3","volume":"7","author":"YM Efremov","year":"2017","unstructured":"Efremov, Y. M., Wang, W.-H., Hardy, S. D., Geahlen, R. L. & Raman, A. Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves. Sci. Rep. 7, 1541 (2017).","journal-title":"Sci. Rep."},{"key":"31_CR33","doi-asserted-by":"publisher","first-page":"21914","DOI":"10.1103\/PhysRevE.72.021914","volume":"72","author":"F Rico","year":"2005","unstructured":"Rico, F. et al. Probing mechanical properties of living cells by atomic force microscopy with blunted pyramidal cantilever tips. Phys. Rev. E 72, 21914 (2005).","journal-title":"Phys. Rev. E"},{"key":"31_CR34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S0091-679X(02)68005-7","volume":"68","author":"M Radmacher","year":"2002","unstructured":"Radmacher, M. Measuring the elastic properties of living cells by the atomic force microscope. Methods Cell Biol. 68, 67\u201390 (2002).","journal-title":"Methods Cell Biol."},{"key":"31_CR35","doi-asserted-by":"publisher","first-page":"12051","DOI":"10.1039\/C7NR03419A","volume":"9","author":"PD Garcia","year":"2017","unstructured":"Garcia, P. D., Guerrero, C. R. & Garcia, R. Time-resolved nanomechanics of a single cell under the depolymerization of the cytoskeleton. Nanoscale 9, 12051\u201312059 (2017).","journal-title":"Nanoscale"},{"key":"31_CR36","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.bpj.2016.12.032","volume":"112","author":"BR Br\u00fcckner","year":"2017","unstructured":"Br\u00fcckner, B. R., N\u00f6ding, H. & Janshoff, A. Viscoelastic properties of confluent MDCK II cells obtained from force cycle experiments. Biophys. J. 112, 724\u2013735 (2017).","journal-title":"Biophys. J."},{"key":"31_CR37","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1038\/nnano.2011.186","volume":"6","author":"A Raman","year":"2011","unstructured":"Raman, A. et al. Mapping nanomechanical properties of live cells using multi-harmonic atomic force microscopy. Nat. Nanotechnol. 6, 809\u2013814 (2011).","journal-title":"Nat. Nanotechnol."},{"key":"31_CR38","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.sna.2003.11.031","volume":"114","author":"O Sahin","year":"2004","unstructured":"Sahin, O. et al. High-resolution imaging of elastic properties using harmonic cantilevers. Sens. Actuators A Phys. 114, 183\u2013190 (2004).","journal-title":"Sens. Actuators A Phys."},{"key":"31_CR39","doi-asserted-by":"publisher","first-page":"7101","DOI":"10.1021\/la990459a","volume":"15","author":"SJT Noort van","year":"1999","unstructured":"van Noort, S. J. T., Willemsen, O. H., van der Werf, K. O., de Grooth, B. G. & Greve, J. Mapping electrostatic forces using higher harmonics tapping mode atomic force microscopy in liquid. Langmuir 15, 7101\u20137107 (1999).","journal-title":"Langmuir"},{"key":"31_CR40","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nnano.2017.45","volume":"12","author":"YF Dufr\u00eane","year":"2017","unstructured":"Dufr\u00eane, Y. F. et al. Imaging modes of atomic force microscopy for application in molecular and cell biology. Nat. Nanotechnol. 12, 295\u2013307 (2017).","journal-title":"Nat. Nanotechnol."},{"key":"31_CR41","doi-asserted-by":"publisher","first-page":"08LA02","DOI":"10.7567\/JJAP.54.08LA02","volume":"54","author":"M Chyasnavichyus","year":"2015","unstructured":"Chyasnavichyus, M., Young, S. L. & Tsukruk, V. V. Recent advances in micromechanical characterization of polymer, biomaterial, and cell surfaces with atomic force microscopy. Jpn. J. Appl. Phys. 54, 08LA02 (2015).","journal-title":"Jpn. J. Appl. Phys."},{"issue":"11","key":"31_CR42","doi-asserted-by":"publisher","first-page":"114905","DOI":"10.1063\/1.3033499","volume":"104","author":"Ryan C. Tung","year":"2008","unstructured":"Tung, R. C., Jana, A. & Raman, A. Hydrodynamic loading of microcantilevers oscillating near rigid walls. J. Appl. Phys. 104, 114905 (2008).","journal-title":"Journal of Applied Physics"},{"key":"31_CR43","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/j.bpj.2013.12.037","volume":"106","author":"A Cartagena","year":"2014","unstructured":"Cartagena, A. & Raman, A. Local viscoelastic properties of live cells investigated using dynamic and quasi-static atomic force microscopy methods. Biophys. J. 106, 1033\u20131043 (2014).","journal-title":"Biophys. J."},{"key":"31_CR44","doi-asserted-by":"publisher","first-page":"4729","DOI":"10.1039\/c3nr34088k","volume":"5","author":"A Cartagena","year":"2013","unstructured":"Cartagena, A., Hernando-P\u00e9rez, M., Carrascosa, J. L., de Pablo, P. J. & Raman, A. Mapping in vitro local material properties of intact and disrupted virions at high resolution using multi-harmonic atomic force microscopy. Nanoscale 5, 4729\u20134736 (2013).","journal-title":"Nanoscale"},{"key":"31_CR45","doi-asserted-by":"publisher","first-page":"13655","DOI":"10.1073\/pnas.0902240106","volume":"106","author":"J Melcher","year":"2009","unstructured":"Melcher, J. et al. Origins of phase contrast in the atomic force microscope in liquids. Proc. Natl. Acad. Sci. USA 106, 13655\u201313660 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"31_CR46","doi-asserted-by":"publisher","first-page":"060801","DOI":"10.1103\/PhysRevLett.102.060801","volume":"102","author":"X Xu","year":"2009","unstructured":"Xu, X., Melcher, J., Basak, S., Reifenberger, R. & Raman, A. Compositional contrast of biological materials in liquids using the momentary excitation of higher eigenmodes in dynamic atomic force microscopy. Phys. Rev. Lett. 102, 060801 (2009).","journal-title":"Phys. Rev. Lett."},{"key":"31_CR47","first-page":"156","volume":"92","author":"H Hertz","year":"1881","unstructured":"Hertz, H. \u00dcber die Ber\u00fchrung Fester Elastischer K\u00f6rper. J. reine u. angew. Math. 92, 156\u2013171 (1881).","journal-title":"J. reine u. angew. Math."},{"key":"31_CR48","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/0020-7225(65)90019-4","volume":"3","author":"IN Sneddon","year":"1965","unstructured":"Sneddon, I. N. The relation between load and penetration in the axisymmetric Boussinesq problem for a punch of arbitrary profile. Int. J. Eng. Sci. 3, 47\u201357 (1965).","journal-title":"Int. J. Eng. Sci."},{"key":"31_CR49","doi-asserted-by":"publisher","first-page":"2798","DOI":"10.1016\/S0006-3495(02)75620-8","volume":"82","author":"EK Dimitriadis","year":"2002","unstructured":"Dimitriadis, E. K., Horkay, F., Maresca, J., Kachar, B. & Chadwick, R. S. Determination of elastic moduli of thin layers of soft material using the atomic force microscope. Biophys. J. 82, 2798\u20132810 (2002).","journal-title":"Biophys. J."},{"key":"31_CR50","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/nnano.2012.163","volume":"7","author":"N Gavara","year":"2012","unstructured":"Gavara, N. & Chadwick, R. S. Determination of the elastic moduli of thin samples and adherent cells using conical atomic force microscope tips. Nat. Nanotechnol. 7, 733\u2013736 (2012).","journal-title":"Nat. Nanotechnol."},{"key":"31_CR51","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1021\/bi500325n","volume":"54","author":"MO Krisenko","year":"2015","unstructured":"Krisenko, M. O., Cartagena, A., Raman, A. & Geahlen, R. L. Nanomechanical property maps of breast cancer cells as determined by multiharmonic atomic force microscopy reveal Syk-dependent changes in microtubule stability mediated by MAP1B. Biochemistry 54, 60\u201368 (2015).","journal-title":"Biochemistry"},{"key":"31_CR52","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/j.bpj.2015.06.066","volume":"109","author":"C Kronlage","year":"2015","unstructured":"Kronlage, C., Sch\u00e4fer-Herte, M., B\u00f6ning, D., Oberleithner, H. & Fels, J. Feeling for filaments: quantification of the cortical actin web in live vascular endothelium. Biophys. J. 109, 687\u2013698 (2015).","journal-title":"Biophys. J."},{"key":"31_CR53","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.micron.2016.03.002","volume":"85","author":"G Smolyakov","year":"2016","unstructured":"Smolyakov, G., Formosa-Dague, C., Severac, C., Duval, R. E. & Dague, E. High speed indentation measures by FV, QI and QNM introduce a new understanding of bionanomechanical experiments. Micron 85, 8\u201314 (2016).","journal-title":"Micron"},{"key":"31_CR54","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/jmr.2510","volume":"29","author":"H Schillers","year":"2016","unstructured":"Schillers, H., Medalsy, I., Hu, S., Slade, A. L. & Shaw, J. E. PeakForce tapping resolves individual microvilli on living cells. J. Mol. Recognit. 29, 95\u2013101 (2016).","journal-title":"J. Mol. Recognit."},{"issue":"3","key":"31_CR55","doi-asserted-by":"publisher","first-page":"3365","DOI":"10.1021\/acsnano.5b07162","volume":"10","author":"Alicia Calzado-Mart\u00edn","year":"2016","unstructured":"Calzado-Mart\u00edn, A., Encinar, M., Tamayo, J., Calleja, M. & San Paulo, A. Effect of actin organization on the stiffness of living breast cancer cells revealed by peak-force modulation atomic force microscopy. ACS Nano (2016). https:\/\/doi.org\/10.1021\/acsnano.5b07162 .","journal-title":"ACS Nano"},{"key":"31_CR56","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s12551-017-0281-7","volume":"9","author":"T Ando","year":"2017","unstructured":"Ando, T. Directly watching biomolecules in action by high-speed atomic force microscopy. Biophys. Rev. 9, 421\u2013429 (2017).","journal-title":"Biophys. Rev."},{"key":"31_CR57","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.ceb.2009.01.002","volume":"21","author":"V Vogel","year":"2009","unstructured":"Vogel, V. & Sheetz, M. P. Cell fate regulation by coupling mechanical cycles to biochemical signaling pathways. Curr. Opin. Cell Biol. 21, 38\u201346 (2009).","journal-title":"Curr. Opin. Cell Biol."},{"key":"31_CR58","doi-asserted-by":"publisher","first-page":"034303","DOI":"10.1063\/1.2767202","volume":"102","author":"X Xu","year":"2007","unstructured":"Xu, X. & Raman, A. Comparative dynamics of magnetically, acoustically, and Brownian motion driven microcantilevers in liquids. J. Appl. Phys. 102, 034303 (2007).","journal-title":"J. Appl. Phys."},{"key":"31_CR59","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1002\/sia.1665","volume":"36","author":"O Enders","year":"2004","unstructured":"Enders, O., Korte, F. & Kolb, H.-A. Lorentz-force-induced excitation of cantilevers for oscillation-mode scanning probe microscopy. Surf. Interface Anal. 36, 119\u2013123 (2004).","journal-title":"Surf. Interface Anal."},{"key":"31_CR60","doi-asserted-by":"publisher","first-page":"013702","DOI":"10.1063\/1.3518965","volume":"82","author":"D Kiracofe","year":"2011","unstructured":"Kiracofe, D., Kobayashi, K., Labuda, A., Raman, A. & Yamada, H. High efficiency laser photothermal excitation of microcantilever vibrations in air and liquids. Rev. Sci. Instrum. 82, 013702 (2011).","journal-title":"Rev. Sci. Instrum."},{"key":"31_CR61","doi-asserted-by":"publisher","first-page":"022136","DOI":"10.1063\/1.3601872","volume":"1","author":"A Labuda","year":"2011","unstructured":"Labuda, A. et al. Comparison of photothermal and piezoacoustic excitation methods for frequency and phase modulation atomic force microscopy in liquid environments. AIP Adv. 1, 022136 (2011).","journal-title":"AIP Adv."},{"key":"31_CR62","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1063\/1.111869","volume":"64","author":"U Rabe","year":"1994","unstructured":"Rabe, U. & Arnold, W. Acoustic microscopy by atomic force microscopy. Appl. Phys. Lett. 64, 1493\u20131495 (1994).","journal-title":"Appl. Phys. Lett."},{"issue":"7","key":"31_CR63","doi-asserted-by":"publisher","first-page":"3622","DOI":"10.1063\/1.363308","volume":"80","author":"T. E. Sch\u00e4ffer","year":"1996","unstructured":"Sch\u00e4ffer, T. E., Cleveland, J. P., Ohnesorge, F., Walters, D. A. & Hansma, P. K. Studies of vibrating atomic force microscope cantilevers in liquid. J. Applied Physics 80, 3622 (2012).","journal-title":"Journal of Applied Physics"},{"key":"31_CR64","doi-asserted-by":"publisher","first-page":"485502","DOI":"10.1088\/0957-4484\/22\/48\/485502","volume":"22","author":"D Kiracofe","year":"2011","unstructured":"Kiracofe, D. & Raman, A. Quantitative force and dissipation measurements in liquids using piezo-excited atomic force microscopy: a unifying theory. Nanotechnology 22, 485502 (2011).","journal-title":"Nanotechnology"},{"key":"31_CR65","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1063\/1.1145130","volume":"65","author":"EL Florin","year":"1994","unstructured":"Florin, E.-L., Radmacher, M., Fleck, B. & Gaub, H. E. Atomic force microscope with magnetic force modulation. Rev. Sci. Instrum. 65, 639 (1994).","journal-title":"Rev. Sci. Instrum."},{"key":"31_CR66","doi-asserted-by":"publisher","first-page":"4111","DOI":"10.1063\/1.117835","volume":"69","author":"W Han","year":"1996","unstructured":"Han, W., Lindsay, S. M. & Jing, T. A magnetically driven oscillating probe microscope for operation in liquids. Appl. Phys. Lett. 69, 4111\u20134113 (1996).","journal-title":"Appl. Phys. Lett."},{"key":"31_CR67","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.ultramic.2006.08.009","volume":"107","author":"G Ge","year":"2007","unstructured":"Ge, G. et al. MAC mode atomic force microscopy studies of living samples, ranging from cells to fresh tissue. Ultramicroscopy 107, 299\u2013307 (2007).","journal-title":"Ultramicroscopy"},{"issue":"5","key":"31_CR68","doi-asserted-by":"publisher","first-page":"053101","DOI":"10.1063\/1.4892075","volume":"105","author":"Andrew Wang","year":"2014","unstructured":"Wang, A., Butte, M. J., Wang, A. & Butte, M. J. Customized atomic force microscopy probe by focused-ion-beam-assisted tip transfer. Appl. Phys. Lett. 105, 053101 (2015).","journal-title":"Applied Physics Letters"},{"key":"31_CR69","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1046\/j.1365-2818.1998.00344.x","volume":"191","author":"E Nagao","year":"1998","unstructured":"Nagao, E. & Dvorak, J. A. An integrated approach to the study of living cells by atomic force microscopy. J. Microsc. 191, 8\u201319 (1998).","journal-title":"J. Microsc."},{"key":"31_CR70","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nnano.2012.38","volume":"7","author":"R Garcia","year":"2012","unstructured":"Garcia, R. & Herruzo, E. T. The emergence of multifrequency force microscopy. Nat. Nanotechnol. 7, 217\u2013226 (2012).","journal-title":"Nat. Nanotechnol."},{"key":"31_CR71","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1016\/j.eurpolymj.2013.03.037","volume":"49","author":"R Garcia","year":"2013","unstructured":"Garcia, R. & Proksch, R. Nanomechanical mapping of soft matter by bimodal force microscopy. Eur. Polym. J. 49, 1897\u20131906 (2013).","journal-title":"Eur. Polym. J."},{"key":"31_CR72","doi-asserted-by":"publisher","first-page":"125502","DOI":"10.1088\/0957-0233\/21\/12\/125502","volume":"21","author":"SD Solares","year":"2010","unstructured":"Solares, S. D. & Chawla, G. Frequency response of higher cantilever eigenmodes in bimodal and trimodal tapping mode atomic force microscopy. Meas. Sci. Technol. 21, 125502 (2010).","journal-title":"Meas. Sci. Technol."},{"key":"31_CR73","doi-asserted-by":"publisher","first-page":"021911","DOI":"10.1103\/PhysRevE.74.021911","volume":"74","author":"M Balland","year":"2006","unstructured":"Balland, M. et al. Power laws in microrheology experiments on living cells: comparative analysis and modeling. Phys. Rev. E 74, 021911 (2006).","journal-title":"Phys. Rev. E"},{"key":"31_CR74","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1016\/S0006-3495(03)75014-0","volume":"84","author":"J Alcaraz","year":"2003","unstructured":"Alcaraz, J. et al. Microrheology of human lung epithelial cells measured by atomic force microscopy. Biophys. J. 84, 2071\u20132079 (2003).","journal-title":"Biophys. J."},{"issue":"8","key":"31_CR75","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nphys4104","volume":"13","author":"Annafrancesca Rigato","year":"2017","unstructured":"Rigato, A., Miyagi, A., Scheuring, S. & Rico, F. High-frequency microrheology reveals cytoskeleton dynamics in living cells. Nat. Phys. (2017). https:\/\/doi.org\/10.1038\/nphys4104 .","journal-title":"Nature Physics"},{"key":"31_CR76","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1146\/annurev-matsci-062910-100351","volume":"41","author":"P Kollmannsberger","year":"2011","unstructured":"Kollmannsberger, P. & Fabry, B. Linear and nonlinear rheology of living cells. Annu. Rev. Mater. Res. 41, 75\u201397 (2011).","journal-title":"Annu. Rev. Mater. Res."},{"key":"31_CR77","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1002\/cm.20466","volume":"67","author":"O Jonas","year":"2010","unstructured":"Jonas, O. & Duschl, C. Force propagation and force generation in cells. Cytoskeleton 67, 555\u2013563 (2010).","journal-title":"Cytoskeleton"},{"key":"31_CR78","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1002\/jmr.868","volume":"21","author":"YR Silberberg","year":"2008","unstructured":"Silberberg, Y. R. et al. Mitochondrial displacements in response to nanomechanical forces. J. Mol. Recognit. 21, 30\u201336 (2008).","journal-title":"J. Mol. Recognit."},{"key":"31_CR79","doi-asserted-by":"publisher","first-page":"065002","DOI":"10.1088\/1478-3975\/10\/6\/065002","volume":"10","author":"M Krause","year":"2013","unstructured":"Krause, M., te Riet, J. & Wolf, K. Probing the compressibility of tumor cell nuclei by combined atomic force\u2013confocal microscopy. Phys. Biol. 10, 065002 (2013).","journal-title":"Phys. Biol."},{"key":"31_CR80","doi-asserted-by":"publisher","first-page":"6052","DOI":"10.1529\/biophysj.108.139139","volume":"95","author":"MJ Rosenbluth","year":"2008","unstructured":"Rosenbluth, M. J., Crow, A., Shaevitz, J. W. & Fletcher, D. A. Slow stress propagation in adherent cells. Biophys. J. 95, 6052\u20136059 (2008).","journal-title":"Biophys. J."},{"key":"31_CR81","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1039\/c2ib20008b","volume":"4","author":"SM Lim","year":"2012","unstructured":"Lim, S.-M., Trzeciakowski, J. P., Sreenivasappa, H., Dangott, L. J. & Trache, A. RhoA-induced cytoskeletal tension controls adaptive cellular remodeling to mechanical signaling. Integr. Biol. 4, 615 (2012).","journal-title":"Integr. Biol."},{"key":"31_CR82","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1002\/jemt.22522","volume":"78","author":"Ka Melzak","year":"2015","unstructured":"Melzak, Ka & Toca-Herrera, J. L. Atomic force microscopy and cells: indentation profiles around the AFM tip, cell shape changes, and other examples of experimental factors affecting modeling. Microsc. Res. Tech. 78, 626\u2013632 (2015).","journal-title":"Microsc. Res. Tech."},{"key":"31_CR83","doi-asserted-by":"publisher","first-page":"034024","DOI":"10.1117\/1.3155517","volume":"14","author":"A Trache","year":"2009","unstructured":"Trache, A. & Lim, S.-M. Integrated microscopy for real-time imaging of mechanotransduction studies in live cells. J. Biomed. Opt. 14, 034024 (2009).","journal-title":"J. Biomed. Opt."},{"key":"31_CR84","doi-asserted-by":"publisher","DOI":"10.1038\/srep19686","volume":"6","author":"JR Staunton","year":"2016","unstructured":"Staunton, J. R., Doss, B. L., Lindsay, S. & Ros, R. Correlating confocal microscopy and atomic force indentation reveals metastatic cancer cells stiffen during invasion into collagen I matrices. Sci. Rep. 6, 19686 (2016).","journal-title":"Sci. Rep."},{"key":"31_CR85","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1002\/jemt.22696","volume":"80","author":"M Cascione","year":"2017","unstructured":"Cascione, M., de Matteis, V., Rinaldi, R. & Leporatti, S. Atomic force microscopy combined with optical microscopy for cells investigation. Microsc. Res. Tech. 80, 109\u2013123 (2017).","journal-title":"Microsc. Res. Tech."},{"key":"31_CR86","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/S0006-3495(02)75214-4","volume":"83","author":"GT Charras","year":"2002","unstructured":"Charras, G. T. & Horton, M. A. Determination of cellular strains by combined atomic force microscopy and finite element modeling. Biophys. J. 83, 858\u2013879 (2002).","journal-title":"Biophys. J."},{"key":"31_CR87","doi-asserted-by":"crossref","first-page":"54","DOI":"10.7171\/jbt.15-2602-003","volume":"26","author":"J Jonkman","year":"2015","unstructured":"Jonkman, J. & Brown, C. M. Any way you slice it-a comparison of confocal microscopy techniques. J. Biomol. Tech. 26, 54\u201365 (2015).","journal-title":"J. Biomol. Tech."},{"key":"31_CR88","doi-asserted-by":"publisher","first-page":"6511","DOI":"10.1021\/jp8103358","volume":"113","author":"V Lulevich","year":"2009","unstructured":"Lulevich, V., Shih, Y. P., Lo, S. H. & Liu, G. Cell tracing dyes significantly change single cell mechanics. J. Phys. Chem. B 113, 6511\u20136519 (2009).","journal-title":"J. Phys. Chem. B"},{"key":"31_CR89","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.jbiomech.2015.12.034","volume":"49","author":"K Sliogeryte","year":"2016","unstructured":"Sliogeryte, K. et al. Differential effects of LifeAct-GFP and actin-GFP on cell mechanics assessed using micropipette aspiration. J. Biomech. 49, 310\u2013317 (2016).","journal-title":"J. Biomech."},{"key":"31_CR90","doi-asserted-by":"publisher","unstructured":"Lee, A. C., Decourt, B. & Suter, D. Neuronal cell cultures from Aplysia for high-resolution imaging of growth cones. J. Vis. Exp. (2008). https:\/\/doi.org\/10.3791\/662 .","DOI":"10.3791\/662"},{"key":"31_CR91","doi-asserted-by":"crossref","unstructured":"Suter, D. M. in Cell Migration. Methods in Molecular Biology (Methods and Protocols) (eds. Wells, C. & Parsons, M.) 65\u201386 (Humana Press, New York, 2011).","DOI":"10.1007\/978-1-61779-207-6_6"},{"key":"31_CR92","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nmeth.2972","volume":"11","author":"G Lukinavi\u010dius","year":"2014","unstructured":"Lukinavi\u010dius, G. et al. Fluorogenic probes for live-cell imaging of the cytoskeleton. Nat. Methods 11, 731\u20133 (2014).","journal-title":"Nat. Methods"},{"key":"31_CR93","unstructured":"Sader, J. E. et al. A virtual instrument to standardise the calibration of atomic force microscope cantilevers. Rev. Sci. Instrum. 87, 093711 (2016)."},{"key":"31_CR94","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05383-0","volume":"7","author":"H Schillers","year":"2017","unstructured":"Schillers, H. et al. Standardized nanomechanical atomic force microscopy procedure (SNAP) for measuring soft and biological samples. Sci. Rep. 7, 5117 (2017).","journal-title":"Sci. Rep."},{"key":"31_CR95","doi-asserted-by":"publisher","first-page":"17289","DOI":"10.1039\/C5NR04274G","volume":"7","author":"M Hernando-P\u00e9rez","year":"2015","unstructured":"Hernando-P\u00e9rez, M. et al. Quantitative nanoscale electrostatics of viruses. Nanoscale 7, 17289\u201317298 (2015).","journal-title":"Nanoscale"},{"key":"31_CR96","doi-asserted-by":"publisher","first-page":"5060","DOI":"10.1016\/j.bpj.2009.03.032","volume":"96","author":"Y Xiong","year":"2009","unstructured":"Xiong, Y., Lee, A. C., Suter, D. M. & Lee, G. U. Topography and nanomechanics of live neuronal growth cones analyzed by atomic force microscopy. Biophys. J. 96, 5060\u20135072 (2009).","journal-title":"Biophys. J."},{"key":"31_CR97","doi-asserted-by":"publisher","first-page":"23610","DOI":"10.1074\/jbc.274.33.23610","volume":"274","author":"C Gallet","year":"1999","unstructured":"Gallet, C. et al. Tyrosine phosphorylation of cortactin associated with Syk accompanies thromboxane analogue-induced platelet shape change. J. Biol. Chem. 274, 23610\u201323616 (1999).","journal-title":"J. Biol. Chem."},{"key":"31_CR98","doi-asserted-by":"publisher","first-page":"3451","DOI":"10.1091\/mbc.e06-12-1114","volume":"18","author":"D Roux Le","year":"2007","unstructured":"Le Roux, D. et al. Syk-dependent actin dynamics regulate endocytic trafficking and processing of antigens internalized through the B-cell receptor. Mol. Biol. Cell 18, 3451\u20133462 (2007).","journal-title":"Mol. Biol. Cell"},{"key":"31_CR99","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s003390051204","volume":"66","author":"F Braet","year":"1998","unstructured":"Braet, F., Rotsch, C., Wisse, E. & Radmacher, M. Comparison of fixed and living liver endothelial cells by atomic force microscopy. Appl. Phys. A Mater. Sci. Process. 66, 575\u2013578 (1998).","journal-title":"Appl. Phys. A Mater. Sci. Process."}],"container-title":["Nature Protocols"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41596-018-0031-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41596-018-0031-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41596-018-0031-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T03:56:54Z","timestamp":1693886214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41596-018-0031-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,14]]},"references-count":99,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["31"],"URL":"https:\/\/doi.org\/10.1038\/s41596-018-0031-8","relation":{},"ISSN":["1754-2189","1750-2799"],"issn-type":[{"value":"1754-2189","type":"print"},{"value":"1750-2799","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,14]]},"assertion":[{"value":"14 September 2018","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}