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Molecular Crowding: Physiologic Sensing and Control

Authors
  • Subramanya, Arohan R.
  • Boyd-Shiwarski, Cary R.
Type
Published Article
Journal
Annual Review of Physiology
Publisher
Annual Reviews
Publication Date
Feb 12, 2024
Volume
86
Pages
429–452
Identifiers
DOI: 10.1146/annurev-physiol-042222-025920
Source
Annual Reviews
Keywords
License
Green

Abstract

The cytoplasm is densely packed with molecules that contribute to its nonideal behavior. Cytosolic crowding influences chemical reaction rates, intracellular water mobility, and macromolecular complex formation. Overcrowding is potentially catastrophic; to counteract this problem, cells have evolved acute and chronic homeostatic mechanisms that optimize cellular crowdedness. Here, we provide a physiology-focused overview of molecular crowding, highlighting contemporary advances in our understanding of its sensing and control. Long hypothesized as a form of crowding-induced microcompartmentation, phase separation allows cells to detect and respond to intracellular crowding through the action of biomolecular condensates, as indicated by recent studies. Growing evidence indicates that crowding is closely tied to cell size and fluid volume, homeostatic responses to physical compression and desiccation, tissue architecture, circadian rhythm, aging, transepithelial transport, and total body electrolyte and water balance. Thus, molecular crowding is a fundamental physiologic parameter that impacts diverse functions extending from molecule to organism.

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