|ABSTRACT: Sorting and trafficking of membrane bound proteins in cells involves their interactions with the underlying cytoskeleton. In recent FIMD experiments with human erythrocytes, a mechanically induced uniform skeletal network density gradient, produced by micopipette aspiration, resulted in unexpected lateral segregation of membrane proteins that are not linked to the membrane skeleton (e.g.. GPI-linked CD-59 and aquaporin-1). The equilibrium density profile for the unlinked proteins was characterized by enrichment of the proteins at both the aspiration cap, where the skeletal network density is the lowest, and at the pipette entrance, where the skeletal network density is the highest, with almost complete depletion of the proteins in the intervening membrane portion. Monte Carlo simulation shows that such an equilibrium density profile can result if non-interacting laterally mobile species experience (1) a constant drift force in the direction of the cap, combined with (2) an increasing diffusivity towards the cap, which acts to drive the molecules in the opposite direction. Both these passive forces can be attributed to steric interaction of the mobile membrane protein with the constant skeletal network density gradient. Thus, it appears that biology has recruited two passive physical phenomenon and placed them in juxtapose to drive lateral segregation of highly mobile proteins.||Figure1
* FIMD of human erythrocytes creates a constant but reversible skeletal density gradient which can act as a protein sorting machine
* Prominent examples of this are highly mobile membrane components which are not linked to the membrane skeleton and show marked lateral segregation
* The lateral segregation of highly mobile membrane components by a
skeletal gradient is likely due to opposing lateral forces recruited by
the cell. The combination of passive physical forces, set in juxtapose,
may be a general mechanism for protein sorting.