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Dissecting Particle Uptake Heterogeneity in a Cell Population Using Bayesian Analysis
Biophysical Journal ( IF 3.2 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.bpj.2020.01.043
Md Shahinuzzaman 1 , Dipak Barua 1
Affiliation  

Individual cells in a solution display variable uptake of nanomaterials, peptides, and nutrients. Such variability reflects their heterogeneity in endocytic capacity. In a recent work, we have shown that the endocytic capacity of a cell depends on its size and surface density of endocytic components (transporters). We also demonstrated that in MDA-MB-231 breast cancer cells, the cell-surface transporter density (n) may decay with cell radius (r) following the power rule n ∼ rα, where α ≈ -1. In this work, we investigate how n and r may independently contribute to the endocytic heterogeneity of a cell population. Our analysis indicates that the smaller cells display more heterogeneity because of the higher stochastic variations in n. By contrast, the larger cells display a more uniform uptake, reflecting less-stochastic variations in n. We provide analyses of these dependencies by establishing a stochastic model. Our analysis reveals that the exponent α in the above relationship is not a constant; rather, it is a random variable whose distribution depends on cell size r. Using Bayesian analysis, we characterize the cell-size-dependent distributions of α that accurately capture the particle uptake heterogeneity of MDA-MB-231 cells.

中文翻译:

使用贝叶斯分析剖析细胞群中的粒子摄取异质性

溶液中的单个细胞显示出对纳米材料、肽和营养物质的不同吸收。这种可变性反映了它们内吞能力的异质性。在最近的一项工作中,我们已经表明细胞的内吞能力取决于其内吞成分(转运蛋白)的大小和表面密度。我们还证明,在 MDA-MB-231 乳腺癌细胞中,细胞表面转运蛋白密度 (n) 可能会按照幂律 n ∼ rα 随细胞半径 (r) 衰减,其中 α ≈ -1。在这项工作中,我们研究了 n 和 r 如何独立地影响细胞群的内吞异质性。我们的分析表明,由于 n 的随机变化较高,较小的细胞显示出更多的异质性。相比之下,较大的细胞显示出更均匀的吸收,反映了 n 的随机变化较小。我们通过建立随机模型来分析这些依赖关系。我们的分析表明,上述关系中的指数 α 不是常数;相反,它是一个随机变量,其分布取决于像元大小 r。使用贝叶斯分析,我们表征了 α 的细胞大小依赖性分布,该分布可准确捕获 MDA-MB-231 细胞的颗粒摄取异质性。
更新日期:2020-04-01
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