Department of Physiology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
School of Mechanical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
J Nanobiotechnology. 2021 Jan 11;19(1):21. doi: 10.1186/s12951-020-00765-5.
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@SiO(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.
Overdose (1.0 μg/µL) treatment with MNPs@SiO(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@SiO(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@SiO(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.
Taken together, our results demonstrated that overdose of MNPs@SiO(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.
由于纳米粒子具有独特的物理和化学性质以及较小的尺寸，因此它们在生物医学应用中越来越多地被使用。然而，它们的生物物理评估和副作用评估仍然具有挑战性。我们通过研究含有异硫氰酸罗丹明 B 的二氧化硅涂层磁性纳米粒子（MNPs@SiO（RITC））对人胚肾 293（HEK293）细胞的生物物理方面的影响，解决了这个问题，例如膜流动性和牵引力。我们通过代谢组学和转录组网络分析的组合，进一步扩展了我们对纳米粒子对细胞的生物物理影响的理解。
MNPs@SiO（RITC）的过量（1.0μg/μL）处理诱导了 HEK293 细胞中的脂质过氧化并降低了膜流动性。此外，HEK293 细胞形态缩小，其纵横比显着降低。我们发现每个牵引力（在微柱中测量）均增加，从而增加了 MNPs@SiO（RITC）处理的 HEK293 细胞中的总牵引力。由于膜流动性降低和牵引力增加，细胞运动速度也显着降低。此外，MNPs@SiO（RITC）处理还会使细胞内三磷酸腺苷（ATP）的水平呈剂量依赖性降低。为了了解细胞中的这些生物物理变化，我们分析了转录组和代谢组学图谱，并生成了代谢转录组学网络，该网络揭示了脂质过氧化，粘着斑，细胞运动以及相关基因和代谢物之间的关系。此外，网络的计算预测表明，脂质过氧化增加，粘着斑和细胞运动受到抑制。
总之，我们的研究结果表明，MNPs@SiO（RITC）的过量会损害细胞运动，然后改变细胞的生物物理特性，从而突出了对纳米粒子诱导的副作用进行生物物理评估的必要性。
