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Disruption of Mechanotransduction in Post-Infarct Cardiac Fibroblasts: A Computer Vision Protocol for the Identification of Cryptic Therapeutic Targets under Simulated Microgravity

作者:João Victor Rocha da Silva · 发表于:Zenodo (CERN European Organization for Nuclear Research) · 年份:2026 · DOI:10.5281/zenodo.22071492 · 研究领域:Cellular Mechanics and Interactions、Spaceflight effects on biology、Elasticity and Material Modeling

Post-infarction cardiac fibrosis remains one of the primary mechanical and pathological drivers of global heart failure, characterized by the replacement of necrotic myocardial tissue with na excessively rigid extracellular matrix that hyperactivates mechanotransduction pathways, such as PIEZO1 ion channels. Although precision cardiology has advanced significantly, current therapeutic approaches remain limited by focusing on static molecular profiles while neglecting the biophysical dimension and dynamic mechanical properties of cardiac fibroblasts. Here, we propose the Mechanobiological Vulnerability Index (MVI)—a scalable computational platform designed to investigate the hypothesis that simulated microgravity induces profound and controlled structural perturbations in the cytoskeleton of cardiac fibroblasts, generating a transient window of structural vulnerability capable of exposing cryptic epitopes and neoantigens normally masked under terrestrial gravity. The methodological strategy integrates experimental models of gravitational unloading via rotating wall bioreactors (RWV) coupled with a hybrid computer vision pipeline, combining U-Net networks for high-precision structural segmentation and Vision Transformers (ViT) to capture complex patterns of morphological deformation and the vector calculation of the strain tensor. The theoretical formulation of the MVI synthesizes the magnitude of plasma membrane deformation, the degree of cytoskeletal disorganization, the supp...