Quantitative Analysis of the Correlation between Cell Size and Cellular Uptake of Particles
Quantitative Analysis of the Correlation between Cell Size and Cellular Uptake of Particles
复制标题
DOI：
10.1016/j.bpj.2018.11.3134
复制
发表时间：
2019-01-22
影响因子：
3.4
通讯作者：
Barua, Dipak
中科院分区：
文献类型：
--
作者：
Khetan, Jawahar;Shahinuzzaman, Md;Barua, Dipak
细胞的大小对于许多功能至关重要，包括细胞通信和与环境的物质交换。这项建模和实验研究的重点是了解细胞的大小如何决定其从环境中吸收纳米级细胞外材料的能力。细胞质膜中的多种机制介导细胞对营养物质、生物分子和颗粒的摄取。这些机制涉及通过内吞成分（例如网格蛋白包被的小凹、液泡和小胞饮囊泡）识别和内化细胞外分子。由于不同大小的细胞对外部资源的需求可能不同，因此这些不同内吞途径的集体作用也应根据细胞大小而变化。在这里，我们使用反应扩散模型分析单细胞数据，以询问 M DA-MB 231 乳腺癌细胞的大小与其摄取纳米粒子的能力之间的一对一映射。我们的分析表明，在反应控制和扩散控制的情况下，细胞摄取与细胞半径呈线性关系。此外，这种线性依赖性对 20-200 nm 范围内的粒径变化不敏感。这个结果是违反直觉的，因为一般看法是细胞摄取与细胞体积（质量）或表面积成正比，因此遵循与细胞半径的立方或平方关系。使用我们的模型进行的进一步分析揭示了这种线性关系背后的潜在机制。
The size of a cell is central to many functions, including cellular communication and exchange of materials with the environment. This modeling and experimental study focused on understanding how the size of a cell determines its ability to uptake nanometer-scale extracellular materials from the environment. Several mechanisms in the cell plasma membrane mediate cellular uptake of nutrients, biomolecules, and particles. These mechanisms involve recognition and internalization of the extracellular molecules via endocytic components, such as clathrin-coated pits, vacuoles, and micropinocytic vesicles. Because the demand for an external resource could be different for cells of different sizes, the collective actions of these various endocytic routes should also vary based on the cell size. Here, using a reaction-diffusion model, we analyze single-cell data to interrogate the one/one mapping between the size of the M DA-MB 231 breast cancer cells and their ability to uptake nanoparticles. Our analysis indicates that under both reaction- and diffusion-controlled regimes, cellular uptake follows a linear relationship with the cell radius. Furthermore, this linear dependency is insensitive to particle size variation within 20-200 nm range. This result is counterintuitive because the general perception is that cellular uptake is proportional to the cell volume (mass) or surface area and hence follow a cubic or square relationship with the cell radius. A further analysis using our model reveals a potential mechanism underlying this linear relationship.