Tae Hwan Shin1, Abdurazak Aman Ketebo2, Da Yeon Lee1, Seungah Lee3, Seong Ho Kang3, Shaherin Basith1, Balachandran Manavalan1, Do Hyeon Kwon4, Sungsu Park5, Gwang Lee6,7. 1. Department of Physiology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea. 2. School of Mechanical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea. 3. Department of Applied Chemistry and Institute of Natural Sciences, Kyung Hee University, Yongin-si, 17104, Republic of Korea. 4. Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Republic of Korea. 5. School of Mechanical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea. nanopark@skku.edu. 6. Department of Physiology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea. glee@ajou.ac.kr. 7. Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Republic of Korea. glee@ajou.ac.kr.
Abstract
BACKGROUND: Nanoparticles 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. RESULTS: Overdose (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. CONCLUSION: Taken 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.
BACKGROUND: Nanoparticles 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 humanembryonic kidney293 (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. RESULTS:Overdose (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. CONCLUSION: Taken 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.
Entities:
Keywords:
Cell movement; Membrane fluidity; Micropillar; Silica-coated magnetic nanoparticles; Traction force
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