Clustering of Major Histocompatibility Complex-Class I Molecules in Healthy and Cancer Colon Cells Revealed from Their Nanomechanical Properties
La Rocca, Rosanna
Perrone Donnorso, Michela
Di Fabrizio, Enzo
KAUST DepartmentPhysical Science and Engineering (PSE) Division
Biological and Environmental Sciences and Engineering (BESE) Division
Embargo End Date2022-03-22
Permanent link to this recordhttp://hdl.handle.net/10754/668238
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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.
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
SponsorsWe 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.
PublisherAmerican Chemical Society (ACS)
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