Connectomics of Bone to Brain-Probing Physical Renderings of Cellular Experience

"Brainless" cells, the living constituents inhabiting all biological materials, exhibit remarkably smart, i.e., stimuli-responsive and adaptive, behavior. The emergent spatial and temporal patterns of adaptation, observed as changes in cellular connectivity and tissue remodeling by cells, underpin neuroplasticity, muscle memory, immunological imprinting, and sentience itself, in diverse physiological systems from brain to bone. Connectomics addresses the direct connectivity of cells and cells' adaptation to dynamic environments through manufacture of extracellular matrix, forming tissues and architectures comprising interacting organs and systems of organisms. There is imperative to understand the physical renderings of cellular experience throughout life, from the time of emergence, to growth, adaptation and aging-associated degeneration of tissues. Here we address this need through development of technological approaches that incorporate cross length scale (nm to m) structural data, acquired via multibeam scanning electron microscopy, with machine learning and information transfer using network modeling approaches. This pilot case study uses cutting edge imaging methods for nano- to meso-scale study of cellular inhabitants within human hip tissue resected during the normal course of hip replacement surgery. We discuss the technical approach and workflow and identify the resulting opportunities as well as pitfalls to avoid, delineating a path for cellular connectomics studies in diverse tissue/organ environments and their interactions within organisms and across species. Finally, we discuss the implications of the outlined approach for neuromechanics and the control of physical behavior and neuromuscular training.