The Flow of Life: Convergent Approaches to Understanding Musculoskeletal Health from Molecular- to Meso-Length Scales.

In the current perspective and review article, we address the human body as a living ecosystem with collecting watersheds and draining hydrosheds; we integrate our discoveries over the past quarter of a century and pose the critical open research questions to be addressed going forward, with the aim to improve cell, tissue, organ and organismal health. First, we address the flow of fluid through the tissues of the musculoskeletal system, after which we describe the interactions of the fluid, at multiple lengths and time scales, with the molecular to macroscopic non-fluid tissue components, discussing bone and tissues in the context of "living" chromatography and/or electrophoresis columns. Thereafter, we discuss the implications of functional barrier integrity, and the effects of cytokines on active barrier function and molecular transport between organ systems, tissue compartments, and within tissues. In addition, we address the fluid and its flow and the multi-physics implications thereof for the living inhabitants of tissues, i.e., the cells. Finally, we describe the implications of the solid and fluid components and the cellular inhabitants on ecosystem health, where the tissues and organs comprise the organism form interacting ecosystems throughout life and in the context of health and disease. By taking convergent approaches to understanding musculoskeletal, human and environmental health (which themselves are interdependent), we hope to pave new paths of innovation and discovery, to improve the lives of our worlds' inhabitants, from the worlds of our bone and joints and bodies to the interacting ecosystems of our Earth to unknown worlds beyond our current understanding.