Predictive Computational Biomechanics of Tau-Mediated Microtubule Collapse in 3D Cerebral Organoids under Simulated Microgravity: A Novel Framework for Early Neurodegeneration Mapping

Current paradigms in neurodegeneration research remain limited by static biochemical analyses, largely neglecting the spatiotemporal biophysical collapse that precedes clinical symptoms in Alzheimer’s disease (AD). Here, we introduce a predictive computational framework bridging spatial biophysics and neurobiology, extending the Mechanobiological Vulnerability Index (MVI) to the central nervous system. Using three-dimensional human cerebral organoids subjected to simulated microgravity via Rotating Wall Bioreactors (RCCS), we model the accelerated structural destabilization of the neuronal cytoskeleton and Tau protein-associated networks. Our hybrid computer vision pipeline integrates high-resolution U-Net semantic segmentation with Vision Transformers (ViT) to solve the Green-Lagrange strain tensors across somatic and axonal membranes. By mathematically synthesizing morphological deformation, microtubule depolymerization, and mechanotransduction suppression, the MVI framework calculates the critical kinetic thresholds governing irreversible structural failure. This protocol establishes a deterministic computational roadmap, transforming cellular mechanical fragility into an actionable predictive marker for early neurodegenerative vulnerability.