Quantitative Analysis of the Correlation between Cell Size and Cellular Uptake of Particles

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 MDA-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.