Multiscale Modeling to Tackle the Complexity of Load-Bearing Organ and Tissue Regulation

The behavior of biological tissues is finely tuned by the translation of nanoscale properties (e.g. molecular composition) into specific microscale ultrastructure (e.g. composite and/or oriented microstructures) and multi-physics properties (e.g. swelling, piezoelectricity, mass transport), shaping functional macroscopic responses to external perturbations, typically at the millimetric scale. The proper function of these multiscale interactions further requires maintenance of the extracellular matrix by cells that are both chemo- and mechano-sensitive. Cells are likely exposed, at the microscopic scale, to specific cues, the quantification of which is cornerstone to improve our holistic and rationale understanding of load-bearing tissue regulation in health and disease. Whereas these cues often emerge from macroscopic external perturbations, the relations between cell micro-environment and macroscopic tissue perturbation within an organ are largely non-affine, resulting from the intricate interaction among organ structures, tissue composition and ultra-structure.

The combination of experimental and clinical evidence with multiscale models and simulations has recently shown to be effective in identifying essential mechanisms through which these interactions influence multi-physics signal transduction and cell behaviour. Moreover, evidence is mounting which indicates strategies to treat degenerative tissue diseases or trauma need to include the effects of mechanical loads from the whole organ, tissue, and cellular /molecular scales. While such a need to consider mechanical loading across scales is key in the management of musculoskeletal disorders, the management of other chronic diseases, or cancer, that affect load-bearing organs and tissues would similarly appear to benefit from unravelling such multiscale interactions.

Computational modelling is the cornerstone of the integration of biological and mechanical effects into comprehensive mechanobiological mechanisms for tissue function regulation over several scales, in health and disease. Important research challenges that need to be overcome now to fully leverage their potential include:

1) Detailed tissue level modelling, including functional anisotropy, scale effects, large deformations, and multi-physics behaviour;
2) Coupling of biomechanical models to systems biology models, e.g. for bottom-up approaches of complex tissue regulation processes; and
3) Top-down simulations to quantify the effects of external perturbations on the structural scale, including the non-affine transfer of external cues to multifactorial cell stimulation.

This Research Topic aims to gather Methods, Hypothesis, Original Research and Review articles from worldwide specialists in the simulation of biomechanics- and mechanobiology-related mechanisms involved in tissue homeostasis regulation and/or in the pathophysiology of specific disorders. It will offer a unique library of knowledge and competencies towards tackling the challenges in computational multiscale biomechanics and mechanobiology for the effective management of disorders in which the mechanical competence of tissues plays a critical role.