Biological consequences of asymmetric hop diffusion in the cell membrane

Abstract

Over the last 30 years, the hop diffusion model has been an important paradigm for interpreting both cell membrane structure and dynamics. The basic premise of the model is that the cell membrane is organized into small domain regions through a combination of multi-component phase-separation and interaction between membrane components and the proximal fibers of the intracellular cytoskeleton and extracellular matrix. The partitioned characteristics of this two-dimensional fluid are thought to impose both steric and hydrodynamic barriers that restrict the free motion of mobile membrane components, save for their occasional passage via hopping from one domain to another. Previous investigations of hop diffusion within the cell membrane have identified the potential for diffusional anisotropy [Jaqaman et al. 2011. Cell, 146(4), pp.593-606]. This work utilizes numerical simulations and develops new analytical theory to provide an approximate quantitative description of such asymmetric compartmentalization. These methods are then used to examine the physical requirements for generation of asymmetric hop diffusion within the membrane before concluding with a discussion of the potential biological consequences of such behavior.