Dissecting Particle Uptake Heterogeneity in a Cell Population Using Bayesian Analysis

Abstract

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 a , where a z À1. 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 a 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 a that accurately capture the particle uptake heterogeneity of MDA-MB-231 cells.

Nanotherapeutic Heterogeneity: Sources, Effects, and Solutions

“…For example, the way nanotherapeutics are administered to cell cultures can strongly influence experimental outcomes, [315] and heterogeneity among cells results in large differences in their propensity to internalize nanomaterials. [316][317][318][319] Studying these heterogeneities, and how they interrelate, will greatly benefit the nanomedicine field.…”

Exogenous Metals Atlas in Spermatozoa at Single-Cell Resolution in Relation to Human Semen Quality

“…The features related to the heterogeneous distribution, including the heterogeneity and prevalence indexes, are important properties of metal accumulation, especially when their total content is very low . The capability of sperm to absorb exogenous metals varies from cell to cell and is influenced by stochastic variations, which could impact the heterogeneous features of exogenous metals in the sperm population. In addition, the accumulation of exogenous metals is related to their exposure level and metabolism behavior in the human body as well as the ability to cross the blood–testis barrier .…”