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bioRxiv · 10.64898/2026.01.29.702626

Rectifying Stress into Structural Memory Drives Specialization in Cells and Adaptive Computational Systems

Abstract

Functional specialization in continuous systems requires balancing adaptation to environmental stress with the preservation of encoded information. Yet, the physical constraints governing how living systems reconcile selective information retention with energetic structural reorganization remain unclear-a trade-off that may offer transferable design rules for adaptive computing. Here we present a unified framework that connects cellular specialization to adaptive machine learning through principles of nonequilibrium optimization. We find that asymmetric fluctuations in key parameters act as tunable drives that, when phase-aligned, are rectified into durable functional specialization. Biologically, we show that in adipose mesenchymal cells, transient nutrient deficits trigger cytosolic pH fluctuations. These oscillations, regulated by the ATP12A proton pump, modulate nuclear compartment dynamics to coordinate mitochondrial specialization and lock in epigenetic memory for phenotype persistence. Notably, modulating ATP12A amplifies these drives, enhancing functional specialization and metabolic homeostasis in disease models. Computationally, we formalize analogous principles using a compositional framework based on operadic algebra, where structural updates act as a topological ratchet converting drive fluctuations into persistent architectures. This reveals a learning regime where gains in predictive information are accompanied by auditable residual costs for non-predictive states and reorganization. As a proof of concept, we deploy a self-organizing machine learning system that discovers latent hierarchy and reconstructs data through adaptive compartment dynamics. We show that internal organization fluctuations increase with residuals, an information-processing ledger guiding adaptive computation. Across both domains, local organization gains are directionally linked to dissipation proxies (pH variance in vivo and residuals in silico), consistent with operation under shared constraints. Overall, this work identifies asymmetric-drive rectification as a fundamental mechanism of adaptive specialization, providing thermodynamically informed design rules for both bioengineering and adaptive AI. One-Sentence SummaryAsymmetric-drive rectification is a fundamental mechanism by which cells and adaptive computational systems convert internal stress into structural memory, encoding functional specialization

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BibTeXRIS

Tuyeras, R. V., Morcuende, A., Llinares, C., Segerstolpe, A., Kellis, M., Femenia, T., Agudelo, L. Z.. 2026-02-01. Rectifying Stress into Structural Memory Drives Specialization in Cells and Adaptive Computational Systems. https://doi.org/10.64898/2026.01.29.702626

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