A review of the diverse applications of bond graphs in biology and physiology

Computational biology and physiology is an interdisciplinary endeavour, requiring input from biologists, physiologists, mathematicians, chemists, engineers and clinicians. These systems are composed of complex phenomena across disparate temporal and spatial scales, and a holistic understanding of system behaviour typically requires the application of advanced multi-scale models. While many modelling techniques have been used, the bond graph (BG) is the only approach for modelling physical systems, where ‘causality’ is represented graphically. Additionally, the BG approach with its intrinsic properties allows the modular construction of models and verifying the conservation of mass and energy algorithmically. The BG approach has been widely used in engineering and, more recently, has been increasingly applied to biology and physiological systems. In this review, we briefly introduce the concepts and strengths of BG modelling. Following this, we review the history of BGs in modelling cellular mechanisms, biochemical reactions and musculoskeletal and cardiovascular systems. Then, current developments in BG software are reviewed, and opportunities and perspectives on the future application of BGs are discussed.