title: A frequency-based hypothesis for mechanically targeting and selectively attacking cancer cells.
abstract: Experimental studies recently performed on single cancer and healthy cells have demonstrated that the former are about 70% softer than the latter, regardless of the cell lines and the measurement technique used for determining the mechanical properties. At least in principle, the difference in cell stiffness might thus be exploited to create mechanical-based targeting strategies for discriminating neoplastic transformations within human cell populations and for designing innovative complementary tools to cell-specific molecular tumour markers, leading to possible applications in the diagnosis and treatment of cancer diseases. With the aim of characterizing and gaining insight into the overall frequency response of single-cell systems to mechanical stimuli (typically low-intensity therapeutic ultrasound), a generalized viscoelastic paradigm, combining classical and spring-pot-based models, is introduced for modelling this problem by neglecting the cascade of mechanobiological events involving the cell nucleus, cytoskeleton, elastic membrane and cytosol. Theoretical results show that differences in stiffness, experimentally observed ex vivo and in vitro, allow healthy and cancer cells to be discriminated, by highlighting frequencies (from tens to hundreds of kilohertz) associated with resonance-like phenomena—prevailing on thermal fluctuations—that could be helpful in targeting and selectively attacking tumour cells.
authors.affiliation: Department of Structures for Engineering and Architecture and Interdisciplinary Research Center for Biomaterials, Polytechnic School, College of Engineering, University of Napoli Federico, II via Claudio 21, 80125 Napoli, Italy fraldi@unina.it.
authors.forename: M
authors.initials: M
authors.lastname: Fraldi
authors.affiliation: Department of Structures for Engineering and Architecture and Interdisciplinary Research Center for Biomaterials, Polytechnic School, College of Engineering, University of Napoli Federico, II via Claudio 21, 80125 Napoli, Italy Department of Civil, Environmental and Mechanical Engineering, University of Trento, via Mesiano 77, 38123 Trento, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cugno
authors.affiliation: Department of Civil, Environmental and Mechanical Engineering, University of Trento, via Mesiano 77, 38123 Trento, Italy Department of Civil and Environmental Engineering, Carnegie Mellon University, Pittsburgh, PA 15213-3890, USA Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213-3890, USA TMHRI-Department of Nanomedicine, The Methodist Hospital Research Institute, 6565 Fannin Street, MS B-490 Houston, TX 77030, USA.
authors.forename: L
authors.initials: L
authors.lastname: Deseri
authors.affiliation: Department of Civil and Environmental Engineering, Carnegie Mellon University, Pittsburgh, PA 15213-3890, USA.
authors.forename: K
authors.initials: K
authors.lastname: Dayal
authors.affiliation: Department of Civil, Environmental and Mechanical Engineering, University of Trento, via Mesiano 77, 38123 Trento, Italy Laboratory of Bio-inspired and Graphene Nanomechanics, Department of Civil, Environmental and Mechanical Engineering, University of Trento, Via Mesiano 77, 38123 Trento, Italy Centre of Materials and Microsystems, Bruno Kessler Foundation, Via Santa Croce 77, 38122 Trento, Italy School of Engineering and Materials Science, Queen Mary University, Mile End Road, London E1 4NS, UK nicola.pugno@unitn.it.
authors.forename: N M
authors.initials: NM
authors.lastname: Pugno
mesh_terms: D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D003599:Cytoskeleton / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004548:Elasticity; D006801:Humans; D008962:Models, Theoretical; D009038:Motion; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D015203:Reproducibility of Results; D013314:Stress, Mechanical; D014732:Vibration; D014783:Viscosity
chemical_list: D014408:Biomarkers, Tumor
keywords: cancer; cell mechanics; ultrasound; viscoelasticity