The more the merrier: effects of macromolecular crowding on the structure and dynamics of biological membranes

FEBS J. 2020 Dec;287(23):5039-5067. doi: 10.1111/febs.15429. Epub 2020 Jun 13.


Proteins are essential and abundant components of cellular membranes. Being densely packed within the limited surface area, proteins fulfil essential tasks for life, which include transport, signalling and maintenance of cellular homeostasis. The high protein density promotes nonspecific interactions, which affect the dynamics of the membrane-associated processes, but also contribute to higher levels of membrane organization. Here, we provide a comprehensive summary of the most recent findings of diverse effects resulting from high protein densities in both living membranes and reconstituted systems and display why the crowding phenomenon should be considered and assessed when studying cellular pathways. Biochemical, biophysical and computational studies reveal effects of crowding on the translational mobility of proteins and lipids, oligomerization and clustering of integral membrane proteins, and also folding and aggregation of proteins at the lipid membrane interface. The effects of crowding pervade to larger length scales, where interfacial and transmembrane crowding shapes the lipid membrane. Finally, we discuss the design and development of fluorescence-based sensors for macromolecular crowding and the perspectives to use those in application to cellular membranes and suggest some emerging topics in studying crowding at biological interfaces.

Keywords: anomalous diffusion; clustering; glycocalyx; intrinsically disordered proteins; membrane dynamics; membrane morphology; phase separation; protein:protein interactions; rafts; sensors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism
  • Humans
  • Macromolecular Substances / chemistry*
  • Macromolecular Substances / metabolism
  • Membrane Lipids / chemistry*
  • Membrane Lipids / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Molecular Conformation


  • Macromolecular Substances
  • Membrane Lipids
  • Membrane Proteins