Mechano-chemical control of enzymatic activity in crowded environments
Abstract
Macromolecular crowding has long been known to alter biochemical equilibria and enzyme kinetics, with reported catalytic activities that may increase, decrease, or vary non-monotonically with crowder concentration. Classical Michaelis--Menten kinetics does not by itself identify which of these responses should occur for a conformationally active enzyme. Here, we develop a minimal non-equilibrium mechano-chemical theory for a fueled enzyme embedded in a bath of passive crowders and uncover a fluctuation-induced effective force dipole acting on the enzyme subunits, akin to a generalized form of dispersion or depletion interaction. Since the preferred conformation of the model enzyme varies through the catalytic cycle, the fluctuation-induced mechanical load affects the relevant kinetic activation barriers and is sufficient to produce both monotonic inhibition and non-monotonic modification of turnover. The framework provides a thermodynamically consistent route for linking crowded environments to catalytic currents, suggesting how mechanical design principles could be leveraged to control enzymatic pathways.
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BibTeX
@misc{chatzittofi2026mechanochemical,
title = {{Mechano-chemical control of enzymatic activity in crowded environments}},
author = {Michalis Chatzittofi and Luca Cocconi and Jakob Metson and Ramin Golestanian},
howpublished = {arXiv},
year = {2026},
month = nov,
doi = {10.48550/arxiv.2611.03239},
eprint = {2611.03239},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2611.03239},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Mechano-chemical control of enzymatic activity in crowded environments
AU - Michalis Chatzittofi
AU - Luca Cocconi
AU - Jakob Metson
AU - Ramin Golestanian
PY - 2026
DA - 2026/11/02
PB - arXiv
DO - 10.48550/arxiv.2611.03239
UR - https://arxiv.org/abs/2611.03239
AB - Macromolecular crowding has long been known to alter biochemical equilibria and enzyme kinetics, with reported catalytic activities that may increase, decrease, or vary non-monotonically with crowder concentration. Classical Michaelis--Menten kinetics does not by itself identify which of these responses should occur for a conformationally active enzyme. Here, we develop a minimal non-equilibrium mechano-chemical theory for a fueled enzyme embedded in a bath of passive crowders and uncover a fluctuation-induced effective force dipole acting on the enzyme subunits, akin to a generalized form of dispersion or depletion interaction. Since the preferred conformation of the model enzyme varies through the catalytic cycle, the fluctuation-induced mechanical load affects the relevant kinetic activation barriers and is sufficient to produce both monotonic inhibition and non-monotonic modification of turnover. The framework provides a thermodynamically consistent route for linking crowded environments to catalytic currents, suggesting how mechanical design principles could be leveraged to control enzymatic pathways.
ER -