Uptake and Cellular Effects of Polymethylmethacrylate on Human Cell Lines

Arthur Braun, Harald Seitz
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Abstract

The usage of plastic and its decomposition products leads to their ubiquitous distribution, resulting in their uptake by all living beings, including humans. Polymethylmethacrylate (PMMA) is known as a biocompatible polymer and is used widely in medicine and dentistry, although recent findings have shown its induction of oxidative stress within cells. Worryingly, hardly any data exist investigating the uptake of PMMA particles by cells, the potential effects of these particles on cells and cell signaling pathways and their contributing factors. We assessed the uptake of PMMA beads via confocal microscopy after their incubation with HEK293, A549 and MRC5 cells. Through cell staining, we localized multiple PMMA beads within the cytosol of cells. No alterations regarding cell growth, cell morphology or cell division were found, implying no short-term toxicity towards human cells. Using a cAMP response element binding protein (CREB)-mediated reporter assay, we assessed whether internalized PMMA nanobeads alter cell signaling pathways after stimulation of the cells. CREB was chosen as a well-described transcription factor involved in various cellular processes. Our data led to the assumption that PMMA nano- and microbeads are internalized via endocytosis and end up in lysosomes within the cell cytosol. We concluded that differences regarding the surface composition of the PMMA nanobeads affect their potential to alter cell signaling. These findings emphasize the key role the surface composition plays regarding microplastics and their risks for human health, whereas the usage of medical-grade PMMA remains safe.
聚甲基丙烯酸甲酯对人类细胞株的吸收和细胞效应
塑料及其分解产物的使用导致它们无处不在,从而被包括人类在内的所有生物所吸收。众所周知,聚甲基丙烯酸甲酯(PMMA)是一种生物相容性聚合物,被广泛应用于医药和牙科领域,但最近的研究结果表明,PMMA 会诱发细胞内的氧化应激。令人担忧的是,几乎没有任何数据调查了细胞对 PMMA 颗粒的吸收、这些颗粒对细胞和细胞信号通路的潜在影响及其诱因。我们通过共聚焦显微镜评估了 PMMA 粒子与 HEK293、A549 和 MRC5 细胞孵育后的吸收情况。通过细胞染色,我们在细胞的细胞质中定位了多个 PMMA 珠。没有发现细胞生长、细胞形态或细胞分裂方面的变化,这意味着对人类细胞没有短期毒性。利用 cAMP 反应元件结合蛋白(CREB)介导的报告实验,我们评估了内化的 PMMA 纳米珠在刺激细胞后是否会改变细胞信号通路。CREB 是一种参与各种细胞过程的转录因子,已被广泛描述。我们的数据表明,PMMA 纳米珠和微珠是通过内吞作用内化的,并最终进入细胞胞浆内的溶酶体。我们的结论是,PMMA 纳米微珠表面成分的不同会影响其改变细胞信号的潜力。这些发现强调了表面成分在微塑料及其对人类健康的风险方面所起的关键作用,而医用级 PMMA 的使用仍然是安全的。
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