Biochemical Reactions in the Crowded and Confined Physiological Environment: Physical Chemistry Meets Synthetic Biology
Proteins and nucleic acids constitute at least 20–30% of the total mass (and volume) of all living organisms without exception. Although local composition may vary widely with location within a given cell and between cells, it is evident that much of the chemistry of life – as opposed to laboratory biochemistry – takes place within media containing a substantial volume fraction of macromolecules. These media are termed “crowded” or “volume-occupied”, rather than “concentrated”, as no single macromolecular species need be concentrated. Moreover, many biological compartments do not consist of a continuous fluid phase, but rather a series of small interstitial elements of fluid, or “pores”, bounded by membranes or other relatively immobile structural elements such as cytoskeletal filaments. Such interstitial volume elements might be likened to the holes in a sponge, except that the characteristic sizes of the “holes” are of the order of tens of nanometers. The soluble macromolecules within these pores are termed “confined” to reflect the discontinuous nature of the fluid phase and the small dimensions of the pores.
KeywordsSynthetic Biology Standard Free Energy Relative Free Energy Exclude Volume Effect Macromolecular Crowding
Research conducted in A.P.M.’s laboratory is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. The author thanks Peter McPhie (NIH) for reviewing drafts of this Commentary.
Research in GR lab is funded by the Spanish Ministry of Science and Innovation (grant BIO2008-04478-C03-03), the Madrid Government (COMBACT_CM), and the EU (HEALTH-F3-2009-223431).
We are grateful to Company of Biologists Ltd., which allowed the reproduction of the full article (Minton 2006).
- Goodsell DS (1993) The machinery of life. Springer, New YorkGoogle Scholar
- Minton AP (1976) Quantitative relations between oxygen saturation and aggregation of sickle-cell hemoglobin: analysis of oxygen binding data. In: Hercules JI, Cottam GL, Waterman MR, Schechter AN (eds) Proceedings of the symposium on molecular and cellular aspects of sickle cell disease, pp 257–273. U.S. Department of Health, Education and Welfare, Bethesda, MDGoogle Scholar
- Minton AP (1989) Holobiochemistry: an integrated approach to the understanding of biochemical mechanism that emerges from the study of proteins and protein associations in volume-occupied solutions. In: Srere P, Jones ME, Mathews C (eds) Structural and Organizational Aspects of Metabolic Regulation. Alan R. Liss, New York, pp 291–306Google Scholar
- Rivas G, Fernandez JA, Minton AP (1999) Direct observation of the self association of dilute proteins in the presence of inert macromolecules at high concentration via tracer sedimentation equilibrium: theory, experiment, and biological significance. Biochemistry 38:9379–9388CrossRefPubMedGoogle Scholar
- Somero GN, Osmond CB, Bolis CL (1992) Water and life. Springer, BerlinGoogle Scholar
- Zhou HX, Rivas G, Minton AP (2008) Annu. Rev. Biophys. 37:375–397Google Scholar