{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T18:36:32Z","timestamp":1772822192906,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T00:00:00Z","timestamp":1587427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/Multi\/04046\/2019"],"award-info":[{"award-number":["UID\/Multi\/04046\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). A single recessive mutation, the deletion of phenylalanine 508 (F508del), causes severe CF and resides on 70% of mutant chromosomes. Disorganization of the actin cytoskeleton has been previously reported in relation to the CF phenotype. In this work, we aimed to understand this alteration by means of Atomic Force Microscopy and Force Feedback Microscopy investigation of mechanical properties of cystic fibrosis bronchial epithelial (CFBE) cells stably transduced with either wild type (wt-) or F508del-CFTR. We show here that the expression of mutant CFTR causes a decrease in the cell\u2019s apparent Young modulus as compared to the expression of the wt protein.<\/jats:p>","DOI":"10.3390\/ijms21082916","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T04:15:13Z","timestamp":1587528913000},"page":"2916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mechanical Properties of Human Bronchial Epithelial Cells Expressing Wt- and Mutant CFTR"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2654-6848","authenticated-orcid":false,"given":"Ana P.","family":"Carapeto","sequence":"first","affiliation":[{"name":"BioISI \u2013 Instituto de Biosistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"},{"name":"Departamento de F\u00edsica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6821-4481","authenticated-orcid":false,"given":"Miguel V.","family":"Vitorino","sequence":"additional","affiliation":[{"name":"BioISI \u2013 Instituto de Biosistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"},{"name":"Departamento de F\u00edsica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5809-0203","authenticated-orcid":false,"given":"Jo\u00e3o D.","family":"Santos","sequence":"additional","affiliation":[{"name":"BioISI \u2013 Instituto de Biosistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-9802","authenticated-orcid":false,"given":"Sofia S.","family":"Ramalho","sequence":"additional","affiliation":[{"name":"BioISI \u2013 Instituto de Biosistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6044-5333","authenticated-orcid":false,"given":"Tiago","family":"Robalo","sequence":"additional","affiliation":[{"name":"BioISI \u2013 Instituto de Biosistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"},{"name":"Departamento de F\u00edsica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0468-1910","authenticated-orcid":false,"given":"M\u00e1rio S.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"BioISI \u2013 Instituto de Biosistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"},{"name":"Departamento de F\u00edsica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5467-1710","authenticated-orcid":false,"given":"Carlos M.","family":"Farinha","sequence":"additional","affiliation":[{"name":"BioISI \u2013 Instituto de Biosistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1126\/science.7543698","article-title":"CFTR as a cAMP-dependent regulator of sodium channels","volume":"269","author":"Stutts","year":"1995","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1183\/09031936.03.00057003","article-title":"New concepts of the pathogenesis of cystic fibrosis lung disease","volume":"23","author":"Boucher","year":"2004","journal-title":"Eur. Respir. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.pharmthera.2005.04.004","article-title":"Macromolecular complexes of cystic fibrosis transmembrane conductance regulator and its interacting partners","volume":"108","author":"Li","year":"2005","journal-title":"Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1021\/bi702209s","article-title":"Misfolding of the cystic fibrosis transmembrane conductance regulator and disease","volume":"47","author":"Cheung","year":"2008","journal-title":"Biochemistry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1146\/annurev.biochem.75.103004.142532","article-title":"CFTR function and prospects for therapy","volume":"77","author":"Riordan","year":"2008","journal-title":"Annu. Rev. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Farinha, C.M. (2018). CFTR and Cystic Fibrosis. CFTR and Cystic Fibrosis, Springer.","DOI":"10.1007\/978-3-319-65494-2"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6309","DOI":"10.1038\/sj.onc.1204774","article-title":"Expanding the role of NHERF, a PDZ-domain containing protein adapter, to growth regulation","volume":"20","author":"Voltz","year":"2001","journal-title":"Oncogene"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1242\/jcs.185629","article-title":"EPAC1 activation by cAMP stabilizes CFTR at the membrane by promoting its interaction with NHERF1","volume":"129","author":"Lobo","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.bbamcr.2006.09.031","article-title":"CFTR surface expression and chloride currents are decreased by inhibitors of N-WASP and actin polymerization","volume":"1773","author":"Ganeshan","year":"2007","journal-title":"Biochim. Et Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.bbamcr.2007.01.004","article-title":"Cell surface dynamics of CFTR: The ins and outs","volume":"1773","author":"Okiyoneda","year":"2007","journal-title":"Biochim. Et Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1091\/mbc.e09-03-0185","article-title":"Na+\/H+ exchanger regulatory factor 1 overexpression-dependent increase of cytoskeleton organization is fundamental in the rescue of F508del cystic fibrosis transmembrane conductance regulator in human airway CFBE41o-cells","volume":"21","author":"Favia","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s42254-018-0001-7","article-title":"Atomic force microscopy-based mechanobiology","volume":"1","author":"Krieg","year":"2018","journal-title":"Nat. Rev. Phys."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.micron.2007.06.011","article-title":"Atomic force microscopy probing of cell elasticity","volume":"38","author":"Kuznetsova","year":"2007","journal-title":"Micron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20140970","DOI":"10.1098\/rsif.2014.0970","article-title":"Investigating cell mechanics with atomic force microscopy","volume":"12","author":"Haase","year":"2015","journal-title":"J. R. Soc. Interface"},{"key":"ref_15","unstructured":"Jones, D.E., and Schott, G.A. (1896). MiSCellane0us PaperS, MaCimillan."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0020-7225(65)90019-4","article-title":"The relation between load and penetration in the axisymmetric Boussinesq problem for a punch of arbitrary profile","volume":"3","author":"Sneddon","year":"1965","journal-title":"Int. J. Eng. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"203105","DOI":"10.1063\/1.4766172","article-title":"Why do atomic force microscopy force curves still exhibit jump to contact?","volume":"101","author":"Rodrigues","year":"2012","journal-title":"Appl. Phys. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1113\/jphysiol.2005.096669","article-title":"Failure of cAMP agonists to activate rescued \u0394F508 CFTR in CFBE41o\u2013airway epithelial monolayers","volume":"569","author":"Bebok","year":"2005","journal-title":"J. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"054309","DOI":"10.1063\/1.4864127","article-title":"System analysis of force feedback microscopy","volume":"115","author":"Rodrigues","year":"2014","journal-title":"J. Appl. Phys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13848","DOI":"10.1038\/s41598-018-32021-0","article-title":"Direct measurement of the capillary condensation time of a water nanobridge","volume":"8","author":"Vitorino","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40580-017-0099-9","article-title":"Mechanical properties of paraformaldehyde-treated individual cells investigated by atomic force microscopy and scanning ion conductance microscopy","volume":"4","author":"Kim","year":"2017","journal-title":"Nano Converg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21946","DOI":"10.1021\/acsami.6b01755","article-title":"Strain Stiffening of Fibrillar Collagen during Individual and Collective Cell Migration Identified by AFM Nanoindentation","volume":"8","author":"Friedl","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E4439","DOI":"10.1073\/pnas.1609731113","article-title":"Spatially patterned matrix elasticity directs stem cell fate","volume":"113","author":"Yang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108221","DOI":"10.1016\/j.abb.2019.108221","article-title":"Changes in spinal cord stiffness in the course of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis","volume":"680","author":"Lis","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16118","DOI":"10.1038\/s41598-019-52604-9","article-title":"Variation of Burkholderia cenocepacia cell wall morphology and mechanical properties during cystic fibrosis lung infection, assessed by atomic force microscopy","volume":"9","author":"Hassan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20930","DOI":"10.1039\/C8NR06146G","article-title":"AFM assessing of nanomechanical fingerprints for cancer early diagnosis and classification: From single cell to tissue level","volume":"10","author":"Stylianou","year":"2018","journal-title":"Nanoscale"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/nnano.2016.52","article-title":"Atomic force microscopy as a tool to evaluate the risk of cardiovascular diseases in patients","volume":"11","author":"Guedes","year":"2016","journal-title":"Nat. Nanotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.yexcr.2016.08.025","article-title":"Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology","volume":"348","author":"Lasalvia","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2013.10.094","article-title":"Mechanism-based inhibition of cancer metastasis with (-)-epigallocatechin gallate","volume":"443","author":"Takahashi","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/j.bbagen.2016.06.010","article-title":"Cell stiffness determined by atomic force microscopy and its correlation with cell motility","volume":"1860","author":"Luo","year":"2016","journal-title":"Biochim. Et Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00424-008-0524-3","article-title":"Elasticity measurement of living cells with an atomic force microscope: Data acquisition and processing","volume":"457","author":"Carl","year":"2008","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3967","DOI":"10.1063\/1.1150021","article-title":"Calibration of rectangular atomic force microscope cantilevers","volume":"70","author":"Sader","year":"1999","journal-title":"Rev. Sci. Instruments"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5117","DOI":"10.1038\/s41598-017-05383-0","article-title":"Standardized nanomechanical atomic force microscopy procedure (SNAP) for measuring soft and biological samples","volume":"7","author":"Schillers","year":"2017","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/8\/2916\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:45:08Z","timestamp":1760363108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/8\/2916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,21]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["ijms21082916"],"URL":"https:\/\/doi.org\/10.3390\/ijms21082916","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,21]]}}}