27 February 2015 Role of disorder in cell membranes and connection with function

Receptor diffusion on a living cell membrane shows diffusivities changes that lead to weak ergodicity breaking.

Weak ergodicity breaking of receptor motion in living cells stemming from random diffusivity in PRX Fundamental biological processes, including the capture of pathogens by membrane receptors, are regulated by molecular transport. A joint collaboration between the ICREA Professors at ICFO Maria Garcia-Parajo and Maciej Lewenstein show that receptor functioning is linked to nonergodic dynamics, which refers to the difference between the properties of a particle and an ensemble of particles. The work has been recently published in Physics Review X.

Molecular transport in living systems regulates numerous processes underlying biological function. Although many cellular components exhibit anomalous diffusion, only recently has the subdiffusive motion been associated with nonergodic behavior. These findings have stimulated new questions for their implications in statistical mechanics and cell biology. Is nonergodicity a common strategy shared by living systems? Which physical mechanisms generate it? What are its implications for biological function?

Experimentalists C. Manzo and J. Torreno-Pina from the Single Molecule Biophotonics group used single-particle tracking to demonstrate that the motion of the pathogen recognition receptor DC-SIGN reveals nonergodic subdiffusion on living-cell membranes. Indeed, the receptor undergoes changes of diffusivity, consistent with the current view of the cell membrane as a highly dynamic and diverse environment. Theoreticians J. Lapeyre and P. Massignan from the Quantum Optics Theory group then developed a model based on ordinary random walk in complex media to explain the experimental data. Importantly, by studying different receptor mutants, the joint team further correlated receptor motion to its molecular structure, thus establishing a strong link between nonergodicity and biological function.

These results underscore the role of disorder in cell membranes and its connection with function regulation. Because of its generality, this approach offers a framework to interpret anomalous transport in other complex media where dynamic heterogeneity might play a major role, such as those found, e.g., in soft condensed matter, geology, and ecology.