Application of Population Dynamics to Study Heterotypic Cell Aggregations in the Near-Wall Region of a Shear Flow

Abstract

Our research focused on the polymorphonuclear neutrophils (PMNs) tethering to the vascular endothelial cells (EC) and the subsequent melanoma cell emboli formation in a shear flow, an important process of tumor cell extravasation from the circulation during metastasis. We applied population balance model based on Smoluchowski coagulation equation to study the heterotypic aggregation between PMNs and melanoma cells in the near-wall region of an in vitro parallel-plate flow chamber, which simulates in vivo cell-substrate adhesion from the vasculatures by combining mathematical modeling and numerical simulations with experimental observations. To the best of our knowledge, a multiscale near-wall aggregation model was developed, for the first time, which incorporated the effects of both cell deformation and general ratios of heterotypic cells on the cell aggregation process. Quantitative agreement was found between numerical predictions and in vitro experiments. The effects of factors, including: intrinsic binding molecule properties, near-wall heterotypic cell concentrations, and cell deformations on the coagulation process, are discussed. Several parameter identification approaches are proposed and validated which, in turn, demonstrate the importance of the reaction coefficient and the critical bond number on the aggregation process.

Generalized local and nonlocal master equations for some stochastic processes

“…For example, researchers used them to study the heterotypic aggregation kinetics of platelets and neutrophils, most notably in the uniform shear field ( [16,17]). In [19,33], we applied it to model the polymorphonuclear neutrophils (PMN) and tumor cell adhesion in nonuniform shear flow in the parallel-plate flow chamber.…”

Multi-scale biological and physical modelling of the tumour micro-environment

“…We hypothesize that statistical model-of-model approaches can be brought to bear, thereby reducing compute times by many orders of magnitude compared to direct scaling to the cell-population. Other workers have proposed population balance and stochastic aggregation methods for coagulation and heterotypic cell adhesion and aggregation [57][58][59]. These methods are both appropriate-for and limited-to aggregation processes.…”

Cellular and Molecular Bioengineering: A Tipping Point

“…Though the importance of cell-cell communication is well established, CMBE research is now framing this communication within a network of new information and interactions. These cellular interactions – and how they are controlled at the molecular level – have been active topics in CMBE [20, 21]. …”