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Review
. 2018 Apr;10(2):241-253.
doi: 10.1007/s12551-017-0347-6. Epub 2017 Dec 12.

Toward an understanding of biochemical equilibria within living cells

Affiliations
Review

Toward an understanding of biochemical equilibria within living cells

Germán Rivas et al. Biophys Rev. 2018 Apr.

Abstract

Four types of environmental effects that can affect macromolecular reactions in a living cell are defined: nonspecific intermolecular interactions, side reactions, partitioning between microenvironments, and surface interactions. Methods for investigating these interactions and their influence on target reactions in vitro are reviewed. Methods employed to characterize conformational and association equilibria in vivo are reviewed and difficulties in their interpretation cataloged. It is concluded that, in order to be amenable to unambiguous interpretation, in vivo studies must be complemented by in vitro studies carried out in well-characterized and controllable media designed to contain key elements of selected intracellular microenvironments.

Keywords: Association equilibria; Conformational equilibria; Excluded volume; Intermolecular interactions; Macromolecular crowding; Partitioning; Surface interactions.

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Conflict of interest statement

Conflict of interest

Germán Rivas declares that he has no conflict of interest. Allen P. Minton declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
A schematic illustration of how noncovalent interactions may be classified along the interaction free energy scale
Fig. 2
Fig. 2
Thermodynamic cycles illustrating the effect of nonspecific interactions on a conformational equilibrium (a) and an association equilibrium (b)
Fig. 3
Fig. 3
Reaction schemes illustrating the effect of side reactions on a conformational equilibrium (a) and an association equilibrium (b)
Fig. 4
Fig. 4
Reaction schemes illustrating the effect of partitioning between microenvironments on a conformational equilibrium (a) and an association equilibrium (b)
Fig. 5
Fig. 5
Reaction schemes illustrating the effect of surface interactions on a conformational equilibrium (a) and an association equilibrium (b)
Fig. 6
Fig. 6
Most current in vitro studies of crowding effects on conformational equilibria and associations of macromolecules are carried out in model systems containing dilute tracer species in a solution of a single concentrated crowding species (lower left). Current in vivo studies of crowding effects on tracer reactions are carried out in intact cells presenting highly complex and poorly characterized microenvironments (upper right). Progress in understanding the origin of crowding effects in vivo requires the construction of model microenvironments of known and characterized composition, in which selected reactions can be studied by selective variation of composition

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