Enhancing Adaptive Physics Refinement Simulations Through the Addition of Realistic Red Blood Cell Counts.

Simulations of cancer cell transport require accurately modeling mm-scale and longer trajectories through a circulatory system containing trillions of deformable red blood cells, whose intercellular interactions require submicron fidelity. Using a hybrid CPU-GPU approach, we extend the advanced physics refinement (APR) method to couple a finely-resolved region of explicitly-modeled red blood cells to a coarsely-resolved bulk fluid domain. We further develop algorithms that: capture the dynamics at the interface of differing viscosities, maintain hematocrit within the cell-filled volume, and move the finely-resolved region and encapsulated cells while tracking an individual cancer cell.

Distributed Acceleration of Adhesive Dynamics Simulations.

Cell adhesion plays a critical role in processes ranging from leukocyte migration to cancer cell transport during metastasis. Adhesive cell interactions can occur over large distances in microvessel networks with cells traveling over distances much greater than the length scale of their own diameter. Therefore, biologically relevant investigations necessitate efficient modeling of large field-of-view domains, but current models are limited by simulating such geometries at the sub-micron scale required to model adhesive interactions which greatly increases the computational requirements for even small domain sizes.

High Performance Adaptive Physics Refinement to Enable Large-Scale Tracking of Cancer Cell Trajectory.

The ability to track simulated cancer cells through the circulatory system, important for developing a mechanistic understanding of metastatic spread, pushes the limits of today's supercomputers by requiring the simulation of large fluid volumes at cellular-scale resolution. To overcome this challenge, we introduce a new adaptive physics refinement (APR) method that captures cellular-scale interaction across large domains and leverages a hybrid CPU-GPU approach to maximize performance. Through algorithmic advances that integrate multi-physics and multi-resolution models, we establish a finely resolved window with explicitly modeled cells coupled to a coarsely resolved bulk fluid domain.

The role of adhesive receptor patterns on cell transport in complex microvessels.

Cell transport is governed by the interaction of fluid dynamic forces and biochemical factors such as adhesion receptor expression and concentration. Although the effect of endothelial receptor density is well understood, it is not clear how the spacing and local spatial distribution of receptors affect cell adhesion in three-dimensional microvessels. To elucidate the effect of vessel shape on cell trajectory and the arrangement of endothelial receptors on cell adhesion, we employed a three-dimensional deformable cell model that incorporates microscale interactions between the cell and the endothelium.

Computational models of cancer cell transport through the microcirculation.

The transport of cancerous cells through the microcirculation during metastatic spread encompasses several interdependent steps that are not fully understood. Computational models which resolve the cellular-scale dynamics of complex microcirculatory flows offer considerable potential to yield needed insights into the spread of cancer as a result of the level of detail that can be captured. In recent years, in silico methods have been developed that can accurately and efficiently model the circulatory flows of cancer and other biological cells.

Investigating the Interaction Between Circulating Tumor Cells and Local Hydrodynamics Experiment and Simulations.

Introduction: The biological and mechanical properties of circulating tumor cells (CTCs) in combination with the hemodynamics affect the preference of metastatic sites in the vasculature. Despite the extensive literature on the effects of biological properties on cell adhesion, the effects of hydrodynamic forces on primary attachment remains an active area of research. Using simulations in conjunction with experimentation, we provide new insight into the interplay of CTCs dynamics and local hydrodynamics.

Computational Framework to Evaluate the Hydrodynamics of Cell Scaffold Geometries.

The fluid dynamics of microporous materials are important to many biomedical processes such as cell deposition in scaffold materials, tissue engineering, and bioreactors. Microporous scaffolds are frequently composed of suspensions of beads that have varying topology which, in turn, informs their hydrodynamic properties. Previous work has shown that shear stress distributions can affect the response of cells in microporous environments.

Multi-GPU Immersed Boundary Method Hemodynamics Simulations.

Large-scale simulations of blood flow that resolve the 3D deformation of each comprising cell are increasingly popular owing to algorithmic developments in conjunction with advances in compute capability. Among different approaches for modeling cell-resolved hemodynamics, fluid structure interaction (FSI) algorithms based on the immersed boundary method are frequently employed for coupling separate solvers for the background fluid and the cells within one framework. GPUs can accelerate these simulations; however, both current pre-exascale and future exascale CPU-GPU heterogeneous systems face communication challenges critical to performance and scalability.