Abstract
A broad range of membrane proteins display anomalous diffusion on the cell surface. Different methods provide evidence for obstructed subdiffusion and diffusion on a fractal space, but the underlying structure inducing anomalous diffusion has never been visualized because of experimental challenges. We addressed this problem by imaging the cortical actin at high resolution while simultaneously tracking individual membrane proteins in live mammalian cells. Our data confirm that actin introduces barriers leading to compartmentalization of the plasma membrane and that membrane proteins are transiently confined within actin fences. Furthermore, superresolution imaging shows that the cortical actin is organized into a self-similar meshwork. These results present a hierarchical nanoscale picture of the plasma membrane.
- Received 30 November 2016
DOI:https://doi.org/10.1103/PhysRevX.7.011031
Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.
Published by the American Physical Society
Physics Subject Headings (PhySH)
Popular Summary
Across all biological domains, the cell surface plays several critical roles. In mammalian cells, the surface consists of a lipid membrane that provides a boundary to enclose cell components, controls cellular intake and secretions, and helps transmit environmental signals. For proper physiological function, the proteins within the membrane are segregated and organized into dynamic regions that serve different purposes. At any given moment, however, these proteins move about randomly. Despite such an apparent lack of order, the cell surface organization is tightly regulated, albeit in a fashion that is not well understood. We report a direct visualization of the organization of the cell membrane by the underlying actin cytoskeleton, a complex filament meshwork that spans most of the cell and is one of the main players in membrane organization.
Using superresolution imaging of human embryonic kidney (HEK 293) cells, we simultaneously study the random motion of ion channels on the cell membrane and the dynamic actin meshwork. Actin acts as a transient barrier to protein motion, and it partitions the membrane into compartments of various sizes. Close to the cell membrane, the actin meshwork also forms a statistically self-similar fractal that exhibits similar structural properties at many sizes. This structure enables the compartmentalization of the membrane across multiple length scales.
Direct evidence for the compartmentalization of the cell membrane by an underlying actin meshwork is an important step in mammalian cell biology, and it opens up questions regarding how the cell employs this dynamic organization to respond to outside stimuli and to regulate physiological signals.