The liver is the central metabolic organ in the mammalian body. Numerous in silico models have been constructed to simulate liver functions such as circulation, drug transport, metabolism, and clearance at the organism, organ, lobular, cellular, and molecular levels. Adding to the complexity of the spatial dimension are the vastly different temporal scales: from the membrane transport of drug molecules within milliseconds to viral infection of liver tissues in days or months. In recent years there has been a growing trend in the liver modeling community to integrate models at different spatial and temporal scales. For example, a model for the transport of drugs in sinusoids could be coupled with metabolic kinetics models in hepatocytes, whilst incorporating the heterogeneous distribution of metabolic enzymes and transporters along the metabolic zones in liver lobules. Multiscale liver modeling will benefit from recent developments in Systems Biology and/or Systems Medicine.
This Research Topic is to provide a venue for showcasing the concepts, methodology, experimental data, and computational tools associated with multiscale liver modeling. The main challenge in multiscale modeling is to bridge models at different scales. For example, surgical intervention drastically changes perfusion at the organism level, leading to elevated shear stress at the sinusoidal level, which in turn stimulates liver regeneration. Liver diseases progressing over the course of months affect clearance processes at the time scale of hours. Toxic liver injury occurs at the cellular level but affects the circulation of metabolites at the organism level. In addition to models spanning the different scales, integrating cellular and molecular level models and experimental data are the very core of multiscale liver modeling.
The contributions to the Research Topic include Original Research papers, (Mini) Reviews, and Opinions on liver modeling. The specific topics include:
- Blood flow models for large hepatic vessels and/or sinusoids;
- Liver tissue models and virtual lobule models;
- Imaging and image analysis techniques for revealing microstructure and processes at multiple scales;
- Mechanistic factors underlying liver diseases (e.g., steatosis, fibrosis, cirrhosis, cancer)
Projects at the interface of Biomechanics and Computational Biology can also be considered, including:
- Drug uptake, metabolism, and clearance models;
- Numerical/mathematical methods for bridging models at different temporal and spatial scales;
- Application of Systems Biology and Physiome to multiscale liver modeling.
The liver is the central metabolic organ in the mammalian body. Numerous in silico models have been constructed to simulate liver functions such as circulation, drug transport, metabolism, and clearance at the organism, organ, lobular, cellular, and molecular levels. Adding to the complexity of the spatial dimension are the vastly different temporal scales: from the membrane transport of drug molecules within milliseconds to viral infection of liver tissues in days or months. In recent years there has been a growing trend in the liver modeling community to integrate models at different spatial and temporal scales. For example, a model for the transport of drugs in sinusoids could be coupled with metabolic kinetics models in hepatocytes, whilst incorporating the heterogeneous distribution of metabolic enzymes and transporters along the metabolic zones in liver lobules. Multiscale liver modeling will benefit from recent developments in Systems Biology and/or Systems Medicine.
This Research Topic is to provide a venue for showcasing the concepts, methodology, experimental data, and computational tools associated with multiscale liver modeling. The main challenge in multiscale modeling is to bridge models at different scales. For example, surgical intervention drastically changes perfusion at the organism level, leading to elevated shear stress at the sinusoidal level, which in turn stimulates liver regeneration. Liver diseases progressing over the course of months affect clearance processes at the time scale of hours. Toxic liver injury occurs at the cellular level but affects the circulation of metabolites at the organism level. In addition to models spanning the different scales, integrating cellular and molecular level models and experimental data are the very core of multiscale liver modeling.
The contributions to the Research Topic include Original Research papers, (Mini) Reviews, and Opinions on liver modeling. The specific topics include:
- Blood flow models for large hepatic vessels and/or sinusoids;
- Liver tissue models and virtual lobule models;
- Imaging and image analysis techniques for revealing microstructure and processes at multiple scales;
- Mechanistic factors underlying liver diseases (e.g., steatosis, fibrosis, cirrhosis, cancer)
Projects at the interface of Biomechanics and Computational Biology can also be considered, including:
- Drug uptake, metabolism, and clearance models;
- Numerical/mathematical methods for bridging models at different temporal and spatial scales;
- Application of Systems Biology and Physiome to multiscale liver modeling.
