Mechanobiological response of osteocyte PIEZO1 to induced piezoelectricity of bone matrix

Osteocytes are the main responders to mechanical stimuli and the primary regulators of bone metabolism and homeostasis. Piezo channels are mechanosensitive, nonselective cation channels. This study constructs an osteocyte model with a piezoelectric bone matrix, including lacuna-canalicular system and various mechanosensors, integrating the complex effects of solid field, flow field, and electric field on osteocytes. By applying triaxial dynamic displacement loads, the mechanical signals of seven mechanosensors, namely PIEZO1, integrins, primary cilia, collagen hillocks, processes, actin filaments, and microtubules, were analyzed and compared. It was shown that PIEZO1 on the cell soma underwent greater stress in areas with higher cell membrane stress or lower cytoskeleton density. Curved PIEZO1 (unactivated state) and flat PIEZO1 (activated state) exhibited distinct stress distribution patterns. Specifically, the stress in flat PIEZO1 was approximately 30% higher than that in curved PIEZO1. The blade of curved PIEZO1 experienced the greatest stress, while the ion channel of flat PIEZO1 experienced the greatest stress. The stress of primary cilia has increased by more than 40 Pa when PIEZO1 was nearby. Piezoelectricity significantly increased the fluid shear stress (FSS) and the stress of mechanosensors, and changed the trend of FSS. Notably, the collagen hillock experienced the highest FSS, and the flat PIEZO1 experienced greater FSS than the curved PIEZO1. Additionally, among the seven mechanosensors, collagen hillocks experienced the greatest stress. Furthermore, PIEZO1, primary cilia, and cytoskeletons all exhibited excellent displacement signal amplification capabilities and high sensitivity to piezoelectric signals. In conclusion, this study quantified the electromechanical signals of osteocytes in a complex microenvironment, offering insights into bone’s mechanotransduction mechanism across multiple scales. (Figure presented.)