Development of anomalous diffusion among crowding proteins

TL;DR

This study investigates how crowding proteins in cell membranes cause a transition from normal to anomalous diffusion, revealing the onset and progression of subdiffusive behavior as protein density increases.

Contribution

It provides a systematic experimental framework to analyze the onset of anomalous diffusion in crowded membrane environments using fluorescence correlation spectroscopy.

Findings

Anomalous diffusion begins beyond 5% protein coverage.

Higher packing fractions lead to more pronounced subdiffusion.

The transition exhibits spatial heterogeneities.

Abstract

In cell membranes, proteins and lipids diffuse in a highly crowded and heterogeneous landscape, where aggregates and dense domains of proteins or lipids obstruct the path of diffusing molecules. In general, hindered motion gives rise to anomalous transport, though the nature of the onset of this behavior is still under debate and difficult to investigate experimentally. Here, we present a systematic study where proteins bound to supported lipid membranes diffuse freely in two dimensions, but are increasingly hindered by the presence of other like proteins. In our model system, the surface coverage of the protein avidin on the lipid bilayer is well controlled by varying the concentration of biotinylated lipid anchors. Using fluorescence correlation spectroscopy (FCS), we measure the time correlation function over long times and convert it to the mean-square displacement of the diffusing proteins. Our approach allows for high precision data and a clear distinction between anomalous and normal diffusion. It enables us to investigate the onset of anomalous diffusion, which takes place when the area coverage of membrane proteins increases beyond approximately 5%. This transition region exhibits pronounced spatial heterogeneities. Increasing the packing fraction further, transport becomes more and more anomalous, manifested in a decrease of the exponent of subdiffusion.