Cell culture models of epithelial barriers in the body are widely used to study the permeation of nutrients, drugs, infectious agents and pollutants into the body tissues and circulation. The NCI-H441 cell line cultured at the air-liquid interface mimics certain phenotypic and functional characteristics of the human alveolar epithelium. Here the permeability properties of the NCI-H441 model were characterised and compared against published data using experimental measurements and mathematical modelling. Cells were cultured under air-liquid interface conditions and trans-epithelial electrical resistance (TEER) and apparent permeability (P_app) to sodium fluorescein (MW 383 Da) and fluorescently labelled dextrans (MW 4000–150,000 Da) was measured. It was found that TEER was independent of cell seeding density while P_app decreased with higher seeding density and plateaued beyond a density of 500,000 cells/cm². Using the framework of functional pore analysis, a mathematical model was fitted to P_app values measured in this work as well as previously published datasets from human cell lines and primary human and rat cells. It was found that the air-liquid interface NCI-H441 model most closely matched the primary cell line results in contrast to published data using A549 and liquid-interface NCI-H441 cell cultures, supporting the use of this model to study the permeability of the alveolar epithelium to large molecules.

体内上皮屏障的细胞培养模型被广泛用于研究营养物质、药物、感染因子和污染物对身体组织和循环的渗透。在气液界面培养的 NCI-H441 细胞系模拟了人类肺泡上皮的某些表型和功能特征。在这里，使用实验测量和数学建模对 NCI-H441 模型的渗透率特性进行了表征并与已发布的数据进行了比较。细胞在气液界面条件和跨上皮电阻 (TEER) 和表观通透性 ( P _app) 对荧光素钠 (MW 383 Da) 和荧光标记的葡聚糖 (MW 4000–150,000 Da) 进行了测量。发现 TEER 与细胞接种密度无关，而P _app随着接种密度的增加而降低，并在 500,000 个细胞/cm ²的密度以上达到平稳状态。使用功能性孔隙分析的框架，将数学模型拟合到P _app在这项工作中测量的值以及先前发布的来自人类细胞系和原代人类和大鼠细胞的数据集。与使用 A549 和液界面 NCI-H441 细胞培养物的已发表数据相比，气液界面 NCI-H441 模型与原代细胞系结果最接近，支持使用该模型研究细胞的渗透性。肺泡上皮为大分子。