title: Strain-rate Dependence of Elastic Modulus Reveals Silver Nanoparticle Induced Cytotoxicity.
abstract: Force-displacement measurements are taken at different rates with an atomic force microscope to assess the correlation between cell health and cell viscoelasticity in THP-1 cells that have been treated with a novel drug carrier. A variable indentation-rate viscoelastic analysis, VIVA, is employed to identify the relaxation time of the cells that are known to exhibit a frequency dependent stiffness. The VIVA agrees with a fluorescent viability assay. This indicates that dextran-lysozyme drug carriers are biocompatible and deliver concentrated toxic material (rhodamine or silver nanoparticles) to the cytoplasm of THP-1 cells. By modelling the frequency dependence of the elastic modulus, the VIVA provides three metrics of cytoplasmic viscoelasticity: a low frequency modulus, a high frequency modulus and viscosity. The signature of cytotoxicity by rhodamine or silver exposure is a frequency independent twofold increase in the elastic modulus and cytoplasmic viscosity, while the cytoskeletal relaxation time remains unchanged. This is consistent with the known toxic mechanism of silver nanoparticles, where metabolic stress causes an increase in the rigidity of the cytoplasm. A variable indentation-rate viscoelastic analysis is presented as a straightforward method to promote the self-consistent comparison between cells. This is paramount to the development of early diagnosis and treatment of disease.
authors.affiliation: Department of Materials Science Engineering, University of Pennsylvania, Pennsylvania, USA.
authors.forename: Matthew Alexander
authors.initials: MA
authors.lastname: Caporizzo
authors.affiliation: Department of Materials Science Engineering, University of Pennsylvania, Pennsylvania, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Roco
authors.affiliation: Department of Materials Science Engineering, University of Pennsylvania, Pennsylvania, USA; Department of Anesthesiology and Critical Care, University of Pennsylvania, Pennsylvania, USA.
authors.forename: Maria Carme Coll
authors.initials: MC
authors.lastname: Ferrer
authors.affiliation: Department of Materials Science Engineering, University of Pennsylvania, Pennsylvania, USA; Department of Anesthesiology and Critical Care, University of Pennsylvania, Pennsylvania, USA.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Grady
authors.affiliation: Department of Materials Science Engineering, University of Pennsylvania, Pennsylvania, USA.
authors.forename: Emmabeth
authors.initials: E
authors.lastname: Parrish
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, Pennsylvania, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Eckmann
authors.affiliation: Department of Materials Science Engineering, University of Pennsylvania, Pennsylvania, USA.
authors.forename: Russell John
authors.initials: RJ
authors.lastname: Composto
keywords: VIVA; cell viscoelasticity; dextran; elastic modulus; nano-indentation; nanogel; silver cytotoxicity; silver nanoparticle; standard linear solid model; strain-rate dependent elasticity
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