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Autori principali: Terradot, Guillaume, Danos, Vincent
Natura: Preprint
Pubblicazione: 2026
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Accesso online:https://arxiv.org/abs/2604.15296
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author Terradot, Guillaume
Danos, Vincent
author_facet Terradot, Guillaume
Danos, Vincent
contents All cells must sustain ionic motive forces (IMFs) -- the electrochemical gradients of permeant ions, together with the membrane potential they produce -- to regulate intracellular pH, drive secondary transport, and power ATP synthesis. Because membranes are imperfectly impermeable, IMFs continuously dissipate through passive leakage, and active transport must compensate at an energetic cost that competes with growth and biosynthesis. How environmental conditions set this cost, and why cells across the tree of life share a common ionic logic yet deploy strikingly diverse transporter repertoires, has lacked a unifying quantitative account. Here we derive a thermodynamic lower bound on the power required to maintain IMFs at steady state. The bound equals the rate of free-energy dissipation by ion leakage, holds across a broad family of electrophysiological models, and is independent of organism, energy source, or transporter architecture. Cost minimization recovers, from first principles, the universal K+-rich, Na+-poor cytoplasm observed across taxa: asymmetric membrane permeabilities alone are sufficient to explain it. The same framework predicts that extremophiles face higher maintenance costs under extreme pH, salinity, and temperature, and that when sustaining a large proton motive force becomes prohibitive, cells should shift to metabolic regimes compatible with smaller PMF, providing a thermodynamic rationale for stress-induced metabolic reconfiguration. Finally, we show that perfect energetic efficiency is unattainable in practice, and that this very imperfection, combined with environmental variability, selects for the diversity of transport architectures observed in nature: each architecture is optimal within a discrete regime of environmental constraints.
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publishDate 2026
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spellingShingle Unity and Diversity of Intracellular pH Maintenance Mechanisms
Terradot, Guillaume
Danos, Vincent
Cell Behavior
All cells must sustain ionic motive forces (IMFs) -- the electrochemical gradients of permeant ions, together with the membrane potential they produce -- to regulate intracellular pH, drive secondary transport, and power ATP synthesis. Because membranes are imperfectly impermeable, IMFs continuously dissipate through passive leakage, and active transport must compensate at an energetic cost that competes with growth and biosynthesis. How environmental conditions set this cost, and why cells across the tree of life share a common ionic logic yet deploy strikingly diverse transporter repertoires, has lacked a unifying quantitative account. Here we derive a thermodynamic lower bound on the power required to maintain IMFs at steady state. The bound equals the rate of free-energy dissipation by ion leakage, holds across a broad family of electrophysiological models, and is independent of organism, energy source, or transporter architecture. Cost minimization recovers, from first principles, the universal K+-rich, Na+-poor cytoplasm observed across taxa: asymmetric membrane permeabilities alone are sufficient to explain it. The same framework predicts that extremophiles face higher maintenance costs under extreme pH, salinity, and temperature, and that when sustaining a large proton motive force becomes prohibitive, cells should shift to metabolic regimes compatible with smaller PMF, providing a thermodynamic rationale for stress-induced metabolic reconfiguration. Finally, we show that perfect energetic efficiency is unattainable in practice, and that this very imperfection, combined with environmental variability, selects for the diversity of transport architectures observed in nature: each architecture is optimal within a discrete regime of environmental constraints.
title Unity and Diversity of Intracellular pH Maintenance Mechanisms
topic Cell Behavior
url https://arxiv.org/abs/2604.15296