bioRxivBiophysicsPreprint
Rectifying Stress into Structural Memory Drives Specialization in Cells and Adaptive Computational Systems
Rémy TuyérasiD, Álvaro MorcuendeiD, Claudia Llinares, Åsa SegerstolpeiD, M KellisiD, Teresa FemeníaiD, Leandro Z. AgudeloiD
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
- organism: human
- assay: ATAC-seq
- assay: bulk RNA-seq
- research focus: cell type annotation
- research focus: clustering
- research focus: gene regulatory network inference
- approach: deep learning
- approach: statistical model
- Citations
- 0
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Cellular intelligence: dynamic specialization through non-equilibrium multi-scale compartmentalization
Rémy Tuyéras, Leandro Z. Agudelo, … M Kellis·bioRxiv·Jun 25, 2021
- Optimal Cellular Phenotypic Adaptation in Fluctuating Environments
J. T. George·bioRxiv·Jan 17, 2023
- Effects of Cellular Memory and Adaptation Cost on Optimal Survival in Fluctuating Environments
Paras Jain, Mohit Kumar Jolly, Jason Thomas George·bioRxiv·May 24, 2025
- Ecosystems as adaptive living circuits
Ankit Dhanuka, Avi I. Flamholz, … Akshit Goyal·bioRxiv·Jun 27, 2025
- A closed-loop mathematical structure of mechanics-turnover coupling for mechanical adaptation in living systems
Eiji Matsumoto, Shinji Deguchi·Journal of Theoretical BiologyPeer-reviewed·Aug 12, 2026
- Outsourcing Memory Through Niche Construction
E. D. Lee, J. Flack, D. Krakauer·bioRxiv·Sep 1, 2022