Deviation from Brownian Diffusion on the Living Cell Membrane: Physical and Biological Implications

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Single Molecule Biophotonics


Organization by compartmentalization is a general property of natural systems that efficiently facilitates and orchestrates biological events in space and time. In the last decade, compartmentalization of the plasma membrane of living cells has emerged as a dominant feature present at different spatiotemporal scales and regulating key cell functions. The advent of super-resolution microscopy and single molecule dynamic approaches has allowed the study of the cell membrane with unprecedented levels of details. In particular, single particle tracking (SPT) approaches have revealed that most cell membrane receptors exhibit anomalous diffusion and weak ergodicity breaking. The manifestation of such behavior is directly linked to receptor function and result from the nano- and meso-scale interaction of molecules with their surrounding environment. In this talk, I will discuss evidence for anomalous diffusion on prototypical membrane receptors and will show the direct correlation between these phenomena and receptor function. Moreover, I will describe the combination of SPT at different labelling densities. Low density conditions allow us to reconstruct the mobility of individual receptors and their transient interaction with other molecular partners, while high density labeling conditions provide complementary information on the spatial and temporal length scales of membrane regions re-visited (or forbidden) for receptors. We find that both the diffusion of receptors and the dynamic re-modelling of the molecular environment play key roles regulating receptor function.