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Soft interactions and crowding

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Abstract

The intracellular milieu is complex, heterogeneous and crowded—an environment vastly different from dilute solutions in which most biophysical studies are performed. The crowded cytoplasm excludes about a third of the volume available to macromolecules in dilute solution. This excluded volume is the sum of two parts: steric repulsions and chemical interactions, also called soft interactions. Until recently, most efforts to understand crowding have focused on steric repulsions. Here, we summarize the results and conclusions from recent studies on macromolecular crowding, emphasizing the contribution of soft interactions to the equilibrium thermodynamics of protein stability. Despite their non-specific and weak nature, the large number of soft interactions present under many crowded conditions can sometimes overcome the stabilizing steric, excluded volume effect.

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Notes

  1. Non-specific attractive interactions are fundamentally different from ligand binding, because ligands bind only to N. Application of Le Chatelier’s principle leads to the conclusion that ligand binding stabilizes proteins by favoring N.

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Acknowledgements

Mohona, Conggang and I (G.J.P.) wish Allen a happy birthday, and we hope he has many more. Allen has profoundly affected my research. It started after hearing his lecture at the 1992 Biopolymers Gordon Conference. I remember thinking, “Pioneering stuff. If I earn tenure I want to work in this area.” I did earn tenure, and over 20 years later, I still work in this now-crowded field. I thank Allen for all his help over those years, especially his infinite patience in explaining the subtle and not so subtle aspects of crowding. My wife, Elizabeth, and I are also grateful for the kindness Allen and Sima have shown both on the road and at home. We thank Michael Rubinstein and Edward Samulski for helpful discussion on soft interactions and excluded volume, and Elizabeth Pielak for comments on the manuscript. G.J.P. thanks Science Foundation Ireland for an E.T.S Walton Visitor Award, which supported his stay in Galway where the outline of this review took shape, and Peter Crowley and his group at NUIG for their hospitality. Our research is supported by the National Science Foundation of the United Sates (MCB-1051819) and the National Natural Sciences Foundation of China (21075134 and 21173258).

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Authors and Affiliations

  1. Department of Chemistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599-3290, USA

    Mohona Sarkar & Gary J. Pielak

  2. Department of Biochemistry and Biophysics, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599-3290, USA

    Gary J. Pielak

  3. UNC Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599-3290, USA

    Gary J. Pielak

  4. Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Molecular and Atomic Physics, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, People’s Republic of China

    Conggang Li

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  1. Mohona Sarkar
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  2. Conggang Li
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Correspondence to Gary J. Pielak.

Additional information

Special Issue: Protein–Protein and Protein–Ligand Interactions in Dilute and Crowded Solution Conditions. In Honor of Allen Minton’s 70th Birthday.

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Sarkar, M., Li, C. & Pielak, G.J. Soft interactions and crowding. Biophys Rev 5, 187–194 (2013). https://doi.org/10.1007/s12551-013-0104-4

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