From Molecule to Morphology: A Multiscale Cell-based Mode of Angiogenesis

A.L. Bauer

Los Alamos National Laboratory

TITLE: From Molecule to Morphology: A Multiscale Cell-Based Model of Angiogenesis

ABSTRACT: Tumor-induced angiogenesis is the formation of new blood vessels from existing vasculature in response to chemical signals from a tumor and is the pivotal transition necessary for cancer invasion and metastasis. Although the sequential steps involved in tumor-induced angiogenesis are well known, the interplay between the biochemical and biomechanical mechanisms that affect angiogenesis is largely unresolved. In this talk, I will present a novel multiscale cell-based model of tumor-induced angiogenesis that is the first to simulate emergent vessel branching.

The multiscale model captures dynamics occurring at three distinct time and length scales – the tissue, cellular and intracellular levels – by integrating multiple modeling techniques. At the tissue scale, differential equations are used to describe the diffusion, cellular uptake, and decay of tumor-secreted pro-angiogenic factor (VEGF). At the cellular scale, a discrete lattice Monte Carlo algorithm captures the behavior of cellular agents (growth, adhesion, migration, and death) and the evolving structure of the extracellular matrix. At the intracellular scale, a stochastic Boolean network describes receptor cross-talk and maps extracellular cues to cell phenotype.

I will discuss how numerical simulations of the multiscale model provide insights into the mechanisms controlling vascular formation in the context of anti-angiogenesis cancer treatment strategies. In particular, I will discuss how the topography of the extracellular matrix influences cell migration and vascular structure, and the relationship between external stimuli, cell phenotype, and vascular morphology. The model represents a synthesis of a large body of compartmentalized research on angiogenesis and provides a means for in silico evaluation and design of new approaches for treating cancer and other angiogenesis-dependent diseases.

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