Multiscale Computational Modeling in Vascular Biology: From Molecular Mechanisms to Tissue-Level Structure and Function
Blood vessels exhibit a remarkable ability to adapt in response to sustained alterations in hemodynamic loads and diverse disease processes. Although such adaptations typically manifest at the tissue level, underlying mechanisms exist at cellular and mole
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Abstract Blood vessels exhibit a remarkable ability to adapt in response to sustained alterations in hemodynamic loads and diverse disease processes. Although such adaptations typically manifest at the tissue level, underlying mechanisms exist at cellular and molecular levels. Dramatic technological advances in recent years, including sophisticated theoretical and computational modeling, have enabled significantly increased understanding at tissue, cellular, and molecular levels, yet there has been little attempt to integrate the associated models across these length and time scales. In this chapter, we suggest a new paradigm for identifying strengths and weaknesses of models at different scales and for establishing congruent models that more completely predict vascular adaptations. Specifically, we show the importance of linking intracellular with cellular models and cellular models with tissue level models. In this way, we propose a new approach for
H. N. Hayenga Department of Bioengineering, University of Maryland, College Park, MD, USA e-mail: [email protected] B. C. Thorne P. Yen J. A. Papin S. M. Peirce Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA e-mail: [email protected] P. Yen e-mail: [email protected] J. A. Papin e-mail: [email protected] S. M. Peirce e-mail: [email protected] J. D. Humphrey (&) Department of Biomedical Engineering, Yale University, 55 Prospect Street, MEC 212, New Haven, CT 06520, USA e-mail: [email protected]
Stud Mechanobiol Tissue Eng Biomater (2013) 14: 209–240 DOI: 10.1007/8415_2012_147 Springer-Verlag Berlin Heidelberg 2012 Published Online: 16 September 2012
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incorporating events across these three levels, thus providing a means to predict phenomena that can only emerge from a system of integrated interactions.
1 Introduction: Vascular Biology as a Complex System Vascular development, adaptations to altered hemodynamics, the progression of disease, and responses to injury or clinical treatment—in each of these cases, one can identify tissue-level changes in geometry, structure, function, and properties that result from altered cellular phenotypes, which in turn depend on changes in intracellular signaling pathways. Indeed, our knowledge of the complex web of signals that underpin vascular function, homeostasis, growth, and remodeling at different levels of biological scale is growing exponentially as more sophisticated experimental models, techniques for analysis, and tools for integrating data become available. Recent technological developments in molecular biology and bioinformatics have thus made high-throughput analyses commonplace and ‘‘– omics’’ data widely accessible. The empirical tools we can use to manipulate and measure vascular structure, function, and adaptation in vivo—ranging from inducible genetic manipulations in mice to non-invasive intravital microscopy with single-cell resolution—are more flexible and precise than ever before. Parallel advances in systems biology, ag
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