Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s disease
Red blood cells (RBCs) are characterized by a remarkable elasticity, which allows them to undergo very large deformation when passing through small vessels and capillaries. This extreme deformability is altered in various clinical conditions, suggesting that the analysis of red blood cell (RBC) mech...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.932354/full |
| _version_ | 1828147693272170496 |
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| author | Matteo Nardini Matteo Nardini Gabriele Ciasca Gabriele Ciasca Alessandra Lauria Cristina Rossi Flavio Di Giacinto Flavio Di Giacinto Sabrina Romanò Sabrina Romanò Riccardo Di Santo Massimiliano Papi Massimiliano Papi Valentina Palmieri Valentina Palmieri Giordano Perini Giordano Perini Umberto Basile Francesca D. Alcaro Enrico Di Stasio Alessandra Bizzarro Carlo Masullo Carlo Masullo Marco De Spirito Marco De Spirito |
| author_facet | Matteo Nardini Matteo Nardini Gabriele Ciasca Gabriele Ciasca Alessandra Lauria Cristina Rossi Flavio Di Giacinto Flavio Di Giacinto Sabrina Romanò Sabrina Romanò Riccardo Di Santo Massimiliano Papi Massimiliano Papi Valentina Palmieri Valentina Palmieri Giordano Perini Giordano Perini Umberto Basile Francesca D. Alcaro Enrico Di Stasio Alessandra Bizzarro Carlo Masullo Carlo Masullo Marco De Spirito Marco De Spirito |
| author_sort | Matteo Nardini |
| collection | DOAJ |
| description | Red blood cells (RBCs) are characterized by a remarkable elasticity, which allows them to undergo very large deformation when passing through small vessels and capillaries. This extreme deformability is altered in various clinical conditions, suggesting that the analysis of red blood cell (RBC) mechanics has potential applications in the search for non-invasive and cost-effective blood biomarkers. Here, we provide a comparative study of the mechanical response of RBCs in patients with Alzheimer’s disease (AD) and healthy subjects. For this purpose, RBC viscoelastic response was investigated using atomic force microscopy (AFM) in the force spectroscopy mode. Two types of analyses were performed: (i) a conventional analysis of AFM force–distance (FD) curves, which allowed us to retrieve the apparent Young’s modulus, E; and (ii) a more in-depth analysis of time-dependent relaxation curves in the framework of the standard linear solid (SLS) model, which allowed us to estimate cell viscosity and elasticity, independently. Our data demonstrate that, while conventional analysis of AFM FD curves fails in distinguishing the two groups, the mechanical parameters obtained with the SLS model show a very good classification ability. The diagnostic performance of mechanical parameters was assessed using receiving operator characteristic (ROC) curves, showing very large areas under the curves (AUC) for selected biomarkers (AUC > 0.9). Taken all together, the data presented here demonstrate that RBC mechanics are significantly altered in AD, also highlighting the key role played by viscous forces. These RBC abnormalities in AD, which include both a modified elasticity and viscosity, could be considered a potential source of plasmatic biomarkers in the field of liquid biopsy to be used in combination with more established indicators of the pathology. |
| first_indexed | 2024-04-11T21:03:59Z |
| format | Article |
| id | doaj.art-793414ca18c44c7c8c0804fa23db1a5d |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-11T21:03:59Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-793414ca18c44c7c8c0804fa23db1a5d2022-12-22T04:03:24ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-09-011410.3389/fnagi.2022.932354932354Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s diseaseMatteo Nardini0Matteo Nardini1Gabriele Ciasca2Gabriele Ciasca3Alessandra Lauria4Cristina Rossi5Flavio Di Giacinto6Flavio Di Giacinto7Sabrina Romanò8Sabrina Romanò9Riccardo Di Santo10Massimiliano Papi11Massimiliano Papi12Valentina Palmieri13Valentina Palmieri14Giordano Perini15Giordano Perini16Umberto Basile17Francesca D. Alcaro18Enrico Di Stasio19Alessandra Bizzarro20Carlo Masullo21Carlo Masullo22Marco De Spirito23Marco De Spirito24Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, ItalyFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, ItalyFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyUnitá Operativa Complessa Neuroriabilitazione ad Alta Intensitá, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyDepartment of Laboratory Diagnostic and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, ItalyFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, ItalyFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, ItalyFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, ItalyIstituto dei Sistemi Complessi (ISC), Consiglio Nazionale delle Ricerche (CNR), Rome, ItalyDipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, ItalyFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDepartment of Laboratory Diagnostic and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDepartment of Laboratory Diagnostic and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDepartment of Laboratory Diagnostic and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyUnitáă Operativa Complessa Continuità assistenziale, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyDipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, ItalySezione di Neurologia, Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, ItalyDipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, ItalyFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyRed blood cells (RBCs) are characterized by a remarkable elasticity, which allows them to undergo very large deformation when passing through small vessels and capillaries. This extreme deformability is altered in various clinical conditions, suggesting that the analysis of red blood cell (RBC) mechanics has potential applications in the search for non-invasive and cost-effective blood biomarkers. Here, we provide a comparative study of the mechanical response of RBCs in patients with Alzheimer’s disease (AD) and healthy subjects. For this purpose, RBC viscoelastic response was investigated using atomic force microscopy (AFM) in the force spectroscopy mode. Two types of analyses were performed: (i) a conventional analysis of AFM force–distance (FD) curves, which allowed us to retrieve the apparent Young’s modulus, E; and (ii) a more in-depth analysis of time-dependent relaxation curves in the framework of the standard linear solid (SLS) model, which allowed us to estimate cell viscosity and elasticity, independently. Our data demonstrate that, while conventional analysis of AFM FD curves fails in distinguishing the two groups, the mechanical parameters obtained with the SLS model show a very good classification ability. The diagnostic performance of mechanical parameters was assessed using receiving operator characteristic (ROC) curves, showing very large areas under the curves (AUC) for selected biomarkers (AUC > 0.9). Taken all together, the data presented here demonstrate that RBC mechanics are significantly altered in AD, also highlighting the key role played by viscous forces. These RBC abnormalities in AD, which include both a modified elasticity and viscosity, could be considered a potential source of plasmatic biomarkers in the field of liquid biopsy to be used in combination with more established indicators of the pathology.https://www.frontiersin.org/articles/10.3389/fnagi.2022.932354/fullAlzheimer’s diseasebiomarkerliquid biopsyAFMmechanicsred blood cells |
| spellingShingle | Matteo Nardini Matteo Nardini Gabriele Ciasca Gabriele Ciasca Alessandra Lauria Cristina Rossi Flavio Di Giacinto Flavio Di Giacinto Sabrina Romanò Sabrina Romanò Riccardo Di Santo Massimiliano Papi Massimiliano Papi Valentina Palmieri Valentina Palmieri Giordano Perini Giordano Perini Umberto Basile Francesca D. Alcaro Enrico Di Stasio Alessandra Bizzarro Carlo Masullo Carlo Masullo Marco De Spirito Marco De Spirito Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s disease Frontiers in Aging Neuroscience Alzheimer’s disease biomarker liquid biopsy AFM mechanics red blood cells |
| title | Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s disease |
| title_full | Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s disease |
| title_fullStr | Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s disease |
| title_full_unstemmed | Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s disease |
| title_short | Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s disease |
| title_sort | sensing red blood cell nano mechanics toward a novel blood biomarker for alzheimer s disease |
| topic | Alzheimer’s disease biomarker liquid biopsy AFM mechanics red blood cells |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.932354/full |
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