Investigation of effect of fullerenol on viscoelasticity properties of human hepatocellular carcinoma by AFM-based creep

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Zuobin Wang International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China

Xianping Liua) School of Engineering, University of Warwick, Coventry CV4 7AL, U.K. (Received 15 March 2017; accepted 24 May 2017)

Cellular elasticity is frequently measured to investigate the biomechanical effects of drug treatment, diseases, and aging. In light of the cellular viscosity property exhibited by filament actin networks, this study investigates the viscoelasticity alterations of the human hepatocellular carcinoma (SMMC-7721) cell subjected to fullerenol treatment by means of creep tests realized by atomic force microscopy indentation. An SMMC-7721 cell was first modeled as a sphere and then as a flattened layer with finite thickness. Both Sneddon’s solutions and the Dimitriadis model have been modified to adapt to the viscoelastic situation, which are used to fit the same indentation depth–time curves obtained by creep tests. We find that the SMMC-7721 cell’s creep behavior is well described by the two modified models and the divergence of parameters determined by the two models is justified. By fullerenol treatment, the SMMC-7721 cell exhibits a significant decrease of elastic modulus and viscosity, which is presumably due to the disruption of actin filaments. This work represents a new attempt to understand the alternation of the viscoelastic properties of cancerous cells under the treatment of fullerenol, which has the significance of comprehensively elucidating the biomechanical effects of anticancer agents (such as fullerenol) on cancer cells.

I. INTRODUCTION

Since the discovery of buckminsterfullerene (C60) in 1985, fullerenes have been attracting much attention for its potential function in biomedical areas, e.g., cancer diagnosis and therapy.1 Despite its promising medical prospects, C60 has inferior solubility in aqueous solutions, which prevents its popularity in biological applications.2 However, this issue is circumvented to a great extent by chemical or supramolecular methods, and thus various functionalized fullerenes have been compounded to achieve promising results.3 For example, by adding hydroxyl groups onto fullerene molecules, a fullerene derivative termed as fullerenol [C60(OH)n] is synthesized which exhibits good water solubility and biological compatibility.4,5 Recent work has shown that fullerenol could impact the cytoskeletal structure whose dynamic alterations are correlated with physiological and pathological processes, e.g., cell growth, differentiation, cancer proliferation, Contributing Editor: Jinju Chen a) Address all correspondence to this author. e-mail: [email protected] DOI: 10.1557/jmr.2017.229

metastasis, and apoptosis. Zhou et al.6 indicated that the disruption of the actin cytoskeleton and microtubule network can induce apoptotic events. Johnson-Lyles et al.7 investigated the biological responses of renal proximal tubule cells which are exposed to fullerenol, to find that cell death induced by fullerenol is ass