Mechanistic Timing and Chromatin Torque in Epithelial-Mesenchymal Transition: A Quantitative Biophysical Modeling Study

This preprint introduces a quantitative biophysical framework designed to investigate the early biomechanical and epigenetic dynamics governing Epithelial-Mesenchymal Transition (EMT) in adenocarcinomas. Standard molecular diagnostics primarily rely on macroscopic phenotypic stability and cytoskeletal integrity (such as E-cadherin retention), often overlooking the silent initiation phase of malignant reprogramming. By analyzing early mechanical confinement gradients and transcriptional energy vectors at the 10% initiation interval, this study models the internal structural torque induced by interfacial shear stress prior to visible morphological delamination. Key quantitative findings and deterministic temporal thresholds isolated by the model include: - Detection of an acute compensatory stiffness drift index (19.85%) during the morphologically silent latency phase. - Characterization of the structural-energetic decoupling leading to E-cadherin delamination (structural integrity dropping from 0.8920 to 0.1850) and transcriptional activation of mesenchymal markers such as SNAIL/SLUG (energy vector rising from 0.2350 to 0.9420). - Identification of two critical temporal boundaries measured from initial mechanical-epigenetic torque onset (t_0 = 0.0): 1. Threshold T2 (t = +5.4 Hours): The critical irreversibility boundary defining the maximum therapeutic window for targeted epigenetic or mechanical intervention. 2. Threshold T1 (t = +8.9 Hours): The target coordinate of complete epithelial structural collapse and transition to an invasive mesenchymal phenotype. This work is shared as an open-access theoretical and computational trajectory intended to support experimental validation in 3D cell cultures, live-cell imaging, and mechanobiology research. === SUGGESTED KEYWORDS === Epithelial-Mesenchymal Transition, Chromatin Torque, Mechanobiology, Epigenetic Reprogramming, H3K27 Methylation, Metastatic Initiation, Biophysical Modeling