Abstract
BackgroundNanoparticles are being increasingly used in biomedical applications owing to their unique physical and chemical properties and small size. However, their biophysical assessment and evaluation of side-effects remain challenging. We addressed this issue by investigating the effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate [MNPs@SiO2(RITC)] on biophysical aspects, such as membrane fluidity and traction force of human embryonic kidney 293 (HEK293) cells. We further extended our understanding on the biophysical effects of nanoparticles on cells using a combination of metabolic profiling and transcriptomic network analysis.ResultsOverdose (1.0 μg/µL) treatment with MNPs@SiO2(RITC) induced lipid peroxidation and decreased membrane fluidity in HEK293 cells. In addition, HEK293 cells were morphologically shrunk, and their aspect ratio was significantly decreased. We found that each traction force (measured in micropillar) was increased, thereby increasing the total traction force in MNPs@SiO2(RITC)-treated HEK293 cells. Due to the reduction in membrane fluidity and elevation of traction force, the velocity of cell movement was also significantly decreased. Moreover, intracellular level of adenosine triphosphate (ATP) was also decreased in a dose-dependent manner upon treatment with MNPs@SiO2(RITC). To understand these biophysical changes in cells, we analysed the transcriptome and metabolic profiles and generated a metabotranscriptomics network, which revealed relationships among peroxidation of lipids, focal adhesion, cell movement, and related genes and metabolites. Furthermore, in silico prediction of the network showed increment in the peroxidation of lipids and suppression of focal adhesion and cell movement.ConclusionTaken together, our results demonstrated that overdose of MNPs@SiO2(RITC) impairs cellular movement, followed by changes in the biophysical properties of cells, thus highlighting the need for biophysical assessment of nanoparticle-induced side-effects.
Highlights
Nanoparticles are being increasingly used in biomedical applications owing to their unique physical and chemical properties and small size
A previous study using inductively coupled plasma atomic emission spectrometry showed that approximately 1 05 particles of Magnetic nanoparticles (MNPs)@ SiO2(RITC) per cell were internalised in MCF-7 breast cancer cells [13]
We determined the dosage used in the present study by treating human embryonic kidney 293 (HEK293) cells with MNPs@ SiO2(RITC) at concentrations ranging from 0.01 to 2.0 μg/μL for 12 h and calculating their uptake efficiencies [21]
Summary
Nanoparticles are being increasingly used in biomedical applications owing to their unique physical and chemical properties and small size. Their biophysical assessment and evaluation of side-effects remain challenging. We addressed this issue by investigating the effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate [MNPs@SiO2(RITC)] on biophysical aspects, such as membrane fluidity and traction force of human embryonic kidney 293 (HEK293) cells. Compared with bulk materials, nanoparticles are known to be more reactive and owing to their higher surfaceto-volume ratio might exhibit more side-effects, such. Our current knowledge regarding the effects of nanoparticles on specific physical and mechanobiological aspects of the cell remains insufficient due to limitations in the available analytical methods. Several biocompatible materials, such as silica, polyethyleneimine, and chitosan have been used to coat nanomaterials to both reduce side-effects and confer beneficial properties on bare nanomaterials [11,12,13,14,15,16,17]
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