Shear-induced cell aggregation and disaggregation, governed by specific receptor-ligand binding, play important roles in many biological and biophysical processes. While a lot of studies have focused on elucidating the shear rate and shear stress dependence of cell aggregation, the majority of existing models based on population balance equation (PBE) has rarely dealt with cell aggregation dynamics upon intrinsic molecular kinetics. Here, a kinetic model was developed for further understanding cell aggregation and disaggregation in a linear shear flow. The novelty of the model is that a set of simple equations was constructed by coupling two-body collision theory with receptor-ligand binding kinetics. Two cases of study were employed to validate the model: one is for the homotypic aggregation dynamics of latex beads cross-linked by protein G-IgG binding, and the other is for the heterotypic aggregation dynamics of neutrophils-tumor cells governed by b2-integrin- ligand interactions. It was found that the model fits the data well and the obtained kinetic parameters are consistent with the previous predictions and experimental measurements. Moreover, the decay factor defined biophysically to account for the chemokine- and shear-induced regulation of receptor and/or ligand expression and conformation was compared at molecular and cellular levels. Our results provided a universal framework to quantify the molecular kinetics of receptor-ligand binding in shear-induced cell aggregation dynamics.
All Science Journal Classification (ASJC) codes
- Modeling and Simulation
- Biochemistry, Genetics and Molecular Biology(all)