Osmotic and functional determinants of skeletal biomechanics

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The skeleton and the muscles forming the framework of a living body (the musculoskeletal system) is a product of adaptation at the evolutionary and lifestyle levels. In the wild, an organism's lifestyle is congruous with its evolutionary adaptation. However, in modern Western society, lifestyle is at odds with what humans had been adapting to over millions of years. While we may be concerned with what happens to astronauts under the influence of microgravity, in terms of skeletal fitness, an urban, sedentary and long-living human might indeed be closer to an individual returning from a long spaceflight rather than to a recent historic ancestor routinely engaged in strenuous physical activity as part of their survival strategy. Today, there is a gap between the intensity of mechanical stimuli that our skeletal system has evolved for since the prehistoric time of persistence hunters, versus the lack of mechanical stimulation that is faced by humans in the Western world. This research proposal describes my interests along two axes: the interactions of water with osmotically active macromolecular assemblies, and the long-term cumulative shaping of the 3D architecture of bone tissue. This research will link the effects of physical activity, aging and pH homeostasis to skeletal biomechanics, at both the nanoscale and macroscale levels. At the nanoscale, in connective tissues such as bone, organic and inorganic components interact with ubiquitous water. The amount of rigidly bound interstitial water governs stiffness, toughness and nonlinear viscoelastic behavior of skeletal tissues. However, the amount of bound water depends on interstitial pH, which itself hinges upon respiratory and renal functions, and upon aerobic/anaerobic energy pathways. Quantifying and unraveling these convolved and mutually-compounding effects on tissue micromechanics can be achieved through stepwise investigation of mineralized and unmineralized acellular biomimetic constructs. Our findings can be translated to normal and aging animal models exposed to experimental sedentary and active conditions. At the macroscale, loading of bone is mirrored by the texture of trabecular bone in the joints. Repetitive, predictable loading and/or older age result in pronounced anisotropic (oriented) stress trajectories, as opposed to diverse, unpredictable loading and/or younger age. However, too monotonous habitual loading renders bone tissue overspecialized and unfit for random and unexpected loads. A study of the 3D texture of trabecular bone in knee joint specimens (using µCT scans) of a robust age series spanning 20-90 years will probe the relations amongst anisotropic trabecular texture, function and age. This study on the discrepancy between phylogenetic adaptation (evolutionary design) and ontogenetic adaptation (operation, or lifestyle) is key to understanding the degenerative physical deconditioning that plagues Western societies, especially as longevity increases.