Strain-Rate Dependence of Elastic Modulus Reveals Silver Nanoparticle Induced Cytotoxicity

Caporizzo, Matthew A.; Roco, Charles M.; Ferrer, M. Carme Coll; Grady, Martha E.; Parrish, Emmabeth; Eckmann, David M.; Composto, Russell J.

doi:10.5772/61328

Cited by 21 publications

(19 citation statements)

References 36 publications

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“…For example, prior work shows that Ag nanoparticles are toxic to THP-1 cells resulting in a change in cell viscoelasticity with a two fold increase in complex modulus. 35 The PEG grafted QDs have a hydrodynamic diameter of 10 nm, determined by diffusion in glycerol:water with known viscosity (supplementary materials). QDs entered each cell by microinjection using an Eppendorf Injection system (supplementary materials), which provides a fast introduction (0.5 s) of QDs by pressure-driven injection of small liquid volumes.…”

Section: Resultsmentioning

confidence: 99%

Intracellular nanoparticle dynamics affected by cytoskeletal integrity

et al. 2017

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The cell interior is a crowded chemical space, which limits the diffusion of molecules and organelles within the cytoplasm, affecting the rates of chemical reactions. We provide insight into the relationship between non-specific intracellular diffusion and cytoskeletal integrity. Quantum dots entered the cell through microinjection and their spatial coordinates were captured by tracking their fluorescence signature as they diffused within the cell cytoplasm. Particle tracking revealed significant enhancement in the mobility of biocompatible quantum dots within fibrosarcoma cells versus their healthy counterparts, fibroblasts, as well as in actin destabilized fibroblasts versus untreated fibroblasts. Analyzing the displacement distributions provided insight into how the heterogeneity of the cell cytoskeleton influences intracellular particle diffusion. We demonstrate that intracellular diffusion of non-specific nanoparticles is enhanced by disrupting the actin network, which has implications for drug delivery efficacy and trafficking.

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Section: Resultsmentioning

confidence: 99%

Intracellular nanoparticle dynamics affected by cytoskeletal integrity

et al. 2017

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“…To determine the contribution of stable MTs to cardiomyocyte mechanical properties, transverse indentation was performed at variable speeds to obtain a VE profile of the cell and to extract generalized VE parameters (22). Fig.…”

Section: Depolymerizing or Tyrosinating Mts Similarly Reduces Myocytementioning

confidence: 99%

Microtubules Provide a Viscoelastic Resistance to Myocyte Motion

Caporizzo

Chen

Salomon

et al. 2018

Biophysical Journal

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Background: Microtubules (MTs) buckle and bear load during myocyte contraction, a behavior enhanced by posttranslational detyrosination. This buckling suggests a spring-like resistance against myocyte shortening, which could store energy and aid myocyte relaxation. Despite this visual suggestion of elastic behavior, the precise mechanical contribution of the cardiac MT network remains to be defined. Methods: Here we experimentally and computationally probe the mechanical contribution of stable MTs and their influence on myocyte function. We use multiple approaches to interrogate viscoelasticity and cell shortening in primary murine myocytes in which either MTs are depolymerized or detyrosination is suppressed and use the results to inform a mathematical model of myocyte viscoelasticity. Results: MT ablation by colchicine concurrently enhances both the degree of shortening and speed of relaxation, a finding inconsistent with simple spring-like MT behavior and suggestive of a viscoelastic mechanism. Axial stretch and transverse indentation confirm that MTs increase myocyte viscoelasticity. Specifically, increasing the rate of strain amplifies the MT contribution to myocyte stiffness. Suppressing MT detyrosination with parthenolide or via overexpression of tubulin tyrosine ligase has mechanical consequences that closely resemble colchicine, suggesting that the mechanical impact of MTs relies on a detyrosination-dependent linkage with the myocyte cytoskeleton. Mathematical modeling affirms that alterations in cell shortening conferred by either MT destabilization or tyrosination can be attributed to internal changes in myocyte viscoelasticity. Conclusions: The results suggest that the cardiac MT network regulates contractile amplitudes and kinetics by acting as a cytoskeletal shock-absorber, whereby MTs provide breakable cross-links between the sarcomeric and nonsarcomeric cytoskeleton that resist rapid length changes during both shortening and stretch.

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“…12,[23][24][25][26] Since the application of AFM to living cells, it has readily been adapted to characterize cell topography [27][28] as well as mechanical properties 12,24,[29][30][31] with nanoscale precision. The AFM has been further adapted for microrheology, [32][33] frequency modulation, [34][35] and creep 25,[36][37] experiments to study the viscoelastic properties of various cell lines. Of interest to this work, is the evaluation of elasticity of endothelial cells, [38][39][40][41] fibroblasts, 28,[42][43][44] chondrocytes, 22,[45][46] fibrosarcomas [47][48][49] and hepatocellular carcinoma cells.…”

Section: Introductionmentioning

confidence: 99%

Cell elasticity with altered cytoskeletal architectures across multiple cell types

Grady

Composto

Eckmann

2016

Journal of the Mechanical Behavior of Biomedical Materials

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105

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The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes.

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Strain-Rate Dependence of Elastic Modulus Reveals Silver Nanoparticle Induced Cytotoxicity

Cited by 21 publications

References 36 publications

Intracellular nanoparticle dynamics affected by cytoskeletal integrity

Intracellular nanoparticle dynamics affected by cytoskeletal integrity

Microtubules Provide a Viscoelastic Resistance to Myocyte Motion

Cell elasticity with altered cytoskeletal architectures across multiple cell types

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