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dc.contributor.authorMoretti, Manola
dc.contributor.authorLa Rocca, Rosanna
dc.contributor.authorPerrone Donnorso, Michela
dc.contributor.authorTorre, Bruno
dc.contributor.authorCanale, Claudio
dc.contributor.authorMalerba, Mario
dc.contributor.authorDas, Gobind
dc.contributor.authorSottile, Rosa
dc.contributor.authorGarofalo, Cinzia
dc.contributor.authorAchour, Adnane
dc.contributor.authorKärre, Klas
dc.contributor.authorCarbone, Ennio
dc.contributor.authorDi Fabrizio, Enzo
dc.date.accessioned2021-03-24T11:01:07Z
dc.date.available2021-03-24T11:01:07Z
dc.date.issued2021-03-22
dc.date.submitted2021-01-30
dc.identifier.citationMoretti, M., La Rocca, R., Perrone Donnorso, M., Torre, B., Canale, C., Malerba, M., … Di Fabrizio, E. (2021). Clustering of Major Histocompatibility Complex-Class I Molecules in Healthy and Cancer Colon Cells Revealed from Their Nanomechanical Properties. ACS Nano. doi:10.1021/acsnano.1c00897
dc.identifier.issn1936-0851
dc.identifier.issn1936-086X
dc.identifier.pmid33749234
dc.identifier.doi10.1021/acsnano.1c00897
dc.identifier.urihttp://hdl.handle.net/10754/668238
dc.description.abstractThe activation of the T cell mediated immune response relies on the fine interaction between the T cell receptor on the immune cell and the antigen-presenting major histocompatibility complex (MHC) molecules on the membrane surface of antigen-presenting cells. Both the distribution and quantity of MHC/peptide complexes and their adequate morphological presentation affect the activation of the immune cells. In several types of cancer the immune response is down-regulated due to the low expression of MHC-class I (MHC-I) molecules on the cell's surface, and in addition, the mechanical properties of the membrane seem to play a role. Herein, we investigate the distribution of MHC-I molecules and the related nanoscale mechanical environment on the cell surface of two cell lines derived from colon adenocarcinoma and a healthy epithelial colon reference cell line. Atomic force microscopy (AFM) force spectroscopy analysis using an antibody-tagged pyramidal probe specific for MHC-I molecules and a formula that relates the elasticity of the cell to the energy of adhesion revealed the different population distributions of MHC-I molecules in healthy cells compared to cancer cells. We found that MHC-I molecules are significantly less expressed in cancer cells. Moreover, the local elastic modulus is significantly reduced in cancer cells. We speculate that these results might be related to the proven ability of cancer cells to evade the immune system, not only by reducing MHC-I cell surface expression but also by modifying the local mechanical properties affecting the overall morphology of MHC-I synapse presentation to immune cells.
dc.description.sponsorshipWe acknowledge financial support from European Project SMD FP7-NMP 2800-SMALL-2 (Proposal No. CP-FP 229375-2), from King Abdullah University of Science and Technology OCRF-2014-CRG and OCRF-2016-CRG grants, and the Italian Ministry of Health under Project Nos. GR-2010-2320665 and GR-2010-2311677. We acknowledge the contribution of F.Cella Zanacchi for the fluorescent microscopy measurements and of G. R. Briola for the drawings in Figure 1,a,b and TOC. We acknowledge G. Stassi and M. Todaro from University of Palermo for kindly providing us the AG2D line.
dc.publisherAmerican Chemical Society (ACS)
dc.relation.urlhttps://pubs.acs.org/doi/10.1021/acsnano.1c00897
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acsnano.1c00897.
dc.titleClustering of Major Histocompatibility Complex-Class I Molecules in Healthy and Cancer Colon Cells Revealed from Their Nanomechanical Properties
dc.typeArticle
dc.contributor.departmentPhysical Science and Engineering (PSE) Division
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.identifier.journalACS Nano
dc.rights.embargodate2022-03-22
dc.eprint.versionPost-print
dc.contributor.institutionIstituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
dc.contributor.institutionDepartment of Physics, University of Genova, Via Dodecaneso 33, 16146 Genova, Italy
dc.contributor.institutionDepartment of Physics, Khalifa University, P. O. Box 127788 Abu Dhabi, United Arab Emirates
dc.contributor.institutionKatharine Hsu Lab, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States
dc.contributor.institutionDepartment for Experimental and Clinical Medicine, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
dc.contributor.institutionScience for Life Laboratory, Department of Medicine, Solna, Karolinska Institute, and Division of Infectious Diseases, Karolinska University Hospital, 17176 Solna, Stockholm, Sweden
dc.contributor.institutionDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, Biomedicum Solnavägen 9, 17165 Solna, Stockholm, Sweden
dc.contributor.institutionDipartimento Medicina di Precisione, Università della Campania, via L. De Crecchio, 7, 80138 Naples, Italy
dc.contributor.institutionDepartment of Applied Physics, Polytechnic University of Turin, Corso Duca degli Abruzzi, 24, 10129 Torino, Italy
kaust.personMoretti, Manola
kaust.personTorre, Bruno
kaust.grant.numberOCRF-2014-CRG
kaust.grant.numberOCRF-2016-CRG grants
dc.date.accepted2021-03-15


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