Intracellular Concentration Gradients That Mirror External Gradients in Microfluidic Flows: A Computational Analysis

The generation of stable intracellular concentration gradients is a useful method for local control of cell function, selective manipulation of cellular structures and testing hypotheses related to dynamical intracellular processes. Cell culture in a microfluidic device allows the presentation of a stable gradient of small molecules across a single cell. This method has been used to selectively label mitochondria in portions of the cell, trypsinize specific cellular domains, and trigger receptor-mediated endocytosis in specific portions of the cell. Given the small length scales of a typical cell (similar to 30 mu m) and short cytoplasmic diffusive time scales of small molecules, it is surprising that cells can be labeled locally with this method. Here we developed models to explore the parametric space over which stable intracellular concentration gradients can be maintained in a microfluidic device. We show that gradients can develop and be maintained indefinitely for high rates of mass transfer across the membrane compared with diffusion, that is, for Sherwood number greater than 1. We show how these gradients can result in gradients in ligand-receptor binding and enzyme substrate binding. This analysis can help interpret and design microfluidic experiments for cytoplasmic partitioning.