Competing aggregation and iso-density equilibrium lead to band pattern formation in density gradients

Abstract

Centrifugation of erythrocytes (aka Red Blood Cells, RBCs) in a self-forming Percoll gradient is a protocol often used as a way to sort RBCs by age. However, a pattern formation of discrete bands is systematically observed along the continuous density gradient. Although early studies mentioned that aggregation between cells might modify their spatial distribution, it is debated whether a population with continuous density distribution can form discrete bands. Here, we develop a continuity equation, considering the aggregation of cells with a continuous density distribution, which describes the macroscopic evolution of the RBC volume concentration in a density gradient. The numerical solutions demonstrate that the competition between iso-density distribution and aggregation is sufficient to create band patterns. Our model reproduces the temporal evolution observed in the conventional experimental protocol, but also predicts several types of bifurcation-like behaviors for the steady-state patterns in constant gradients, when the volume fraction and aggregation energy of the cells are varied. We threrefore discovered that the competition between RBC aggregation and iso-density distribution is a novel physical mechanism leading to pattern formation.