Abstract
Cells do not exist in isolation; they continuously act within and react to their environment. And this environment is not static; it continuously adapts and responds to cells. Here, we investigate how vascular structure and function impact emergent cell population behavior using an agent-based model (ABM). Our ABM enables researchers to "mix and match" cell agents, subcellular modules, and microenvironment components ranging from simple nutrient sources to complex, realistic vascular architectures that accurately capture hemodynamics. We use this ABM to highlight the bilateral relationship between cells and nearby vasculature, demonstrate the effect of vascular structure on environmental heterogeneity, and emphasize the non-linear, non-intuitive relationship between vascular function and the behavior of cell populations over time. Our ABM is well suited to characterizing invitro and invivo studies, with applications from basic science to translational synthetic biology and medicine. The model is freely available at https://github.com/bagherilab/ARCADE. Arecord of this paper's transparent peer review process is included in the supplemental information.
Highlights
Biological systems comprise complex, dynamic environments that modulate and respond to heterogeneous cell behaviors
The tumor microenvironment is a notable example of this bilateral relationship, playing a fundamental role in tumor growth and treatment outcomes (Balkwill et al, 2012; Whiteside, 2008; Bissell and Radisky, 2001; Schaaf et al, 2018)
These features enable agent-based model (ABM) to successfully address existing challenges such as understanding how the microenvironment evolves over time and across space during tumor growth/treatment (Balkwill et al, 2012) and capturing the different levels of heterogeneity within the microenvironment (DeClerck et al, 2017)
Summary
Biological systems comprise complex, dynamic environments that modulate and respond to heterogeneous cell behaviors. The tumor microenvironment is a notable example of this bilateral relationship, playing a fundamental role in tumor growth and treatment outcomes (Balkwill et al, 2012; Whiteside, 2008; Bissell and Radisky, 2001; Schaaf et al, 2018). The framework (1) provides high spatial and temporal resolution, (2) incorporates cellular and environmental heterogeneity, and (3) integrates models developed across disciplines These features enable ABMs to successfully address existing challenges such as understanding how the microenvironment evolves over time and across space during tumor growth/treatment (Balkwill et al, 2012) and capturing the different levels of heterogeneity within the microenvironment (DeClerck et al, 2017). ABMs enable a unique, comprehensive approach for investigating the microenvironment as a whole
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