Shahinuzzaman Md, Barua Dipak
Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri.
Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri.
Biophys J. 2020 Apr 7;118(7):1526-1536. doi: 10.1016/j.bpj.2020.01.043. Epub 2020 Feb 12.
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 ∼ r, 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.
溶液中的单个细胞对纳米材料、肽和营养物质的摄取呈现出可变的情况。这种变异性反映了它们在内吞能力方面的异质性。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大小和内吞成分（转运体）的表面密度。我们还证明，在MDA-MB-231乳腺癌细胞中，细胞表面转运体密度（n）可能遵循幂律n ∼ rα，其中α ≈ -1随细胞半径（r）衰减。在这项工作中，我们研究n和r如何独立地导致细胞群体的内吞异质性。我们的分析表明，较小的细胞由于n的随机变化较大而表现出更多的异质性。相比之下，较大的细胞摄取更均匀，反映出n的随机变化较小。我们通过建立一个随机模型来分析这些依赖性。我们的分析表明，上述关系中的指数α不是一个常数；相反，它是一个随机变量，其分布取决于细胞大小r。使用贝叶斯分析，我们描述了α的细胞大小依赖性分布，该分布准确地捕捉了MDA-MB-231细胞的颗粒摄取异质性。
