Multiscale modeling of transport processes in healthy and tumor induced microcirculation
We propose a computational study of blood flow and transport of solutes in healthy and tumor induced microvascular networks by developing and implementing novel multiscale particle methods. The microcirculation in vascular networks is an inherently multiscale phenomenon. The endothelial cell glycocalyx and plasma proteins are nano/micro scale (10-500 nanometers) structures that affect the micro/macro (1 - 100 micrometers) scale transport of fluid and solutes near and through the vessel walls. In turn the flow modification affects through shear stresses the signaling and proliferation of the endothelial cells as well as the dynamics of the Red Blood Cells (RBC) in small capillaries (10 micrometer scale). The multiscale modeling of microcirculation presents a number of methodological challenges that are addressed in this proposal through the use of particle methods. Particle methods provide a unifying formulation for the description of phenomena across different scales and recent progress in molecular models, fast algorithms, and scalable software have enabled simulations using billions of computational elements that can readily describe phenomena at the atomistic (Molecular Dynamics), mesoscopic (Coarse Grained Molecular Dynamics and DPD) and macroscale (SPH and vortex methods). In this project we will build on our combined expertise in modeling of RBC dynamics in flow using experimentally validated multiscale models, on the development of continuum, discrete and hybrid angiogenesis models, and on the capability to implement highly-scalable particle codes on emergent computer architectures. We envision that the present study will enhance our understanding of the relative importance of phenomena associated with transport processes in the microvasculature. The results of the present study will help to quantify transport phenomena in healthy and tumor induced vasculature thus contributing the development of rational strategies for cancer therapy. This project is a joint work with Prof. P. Koumoutsakos from ETHZ.