Toward an understanding of biochemical equilibria within living cells
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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.
KeywordsIntermolecular interactions Excluded volume Macromolecular crowding Surface interactions Partitioning Conformational equilibria Association equilibria
The authors congratulate Prof. Fumio Arisaka on this happy occasion and salute him for his contributions to the development of protein science and physical biochemistry in Japan. A.P.M. also thanks Prof. Arisaka for a long and productive friendship. The research of A.P.M. is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. The research of G.R. is supported by the Spanish government through grants BFU2014-52070-C2-2-P and BFU2016-75471-C2-1-P. G.R. is a member of the CIB Intramural Program “Macromolecular Machines for Better Life” (MACBET). We thank Mercedes Jimenez (CIB-CSIC) for kindly contributing the final version of the figures.
Compliance with ethical standards
Conflict of interest
Germán Rivas declares that he has no conflict of interest. Allen P. Minton declares that he has no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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