On modeling the multiscale mechanobiology of soft tissues: Challenges and progress.

Tissues grow and remodel in response to mechanical cues, extracellular and intracellular signals experienced through various biological events, from the developing embryo to disease and aging. The macroscale response of soft tissues is typically nonlinear, viscoelastic anisotropic, and often emerges from the hierarchical structure of tissues, primarily their biopolymer fiber networks at the microscale. The adaptation to mechanical cues is likewise a multiscale phenomenon. Cell mechanobiology, the ability of cells to transform mechanical inputs into chemical signaling inside the cell, and subsequent regulation of cellular behavior through intra- and inter-cellular signaling networks, is the key coupling at the microscale between the mechanical cues and the mechanical adaptation seen macroscopically. To fully understand mechanics of tissues in growth and remodeling as observed at the tissue level, multiscale models of tissue mechanobiology are essential. In this review, we summarize the state-of-the art modeling tools of soft tissues at both scales, the tissue level response, and the cell scale mechanobiology models. To help the interested reader become more familiar with these modeling frameworks, we also show representative examples. Our aim here is to bring together scientists from different disciplines and enable the future leap in multiscale modeling of tissue mechanobiology.