Optimal microdomain characteristics for nano-scale protein-protein interactions

Dynamic lateral segregation of signaling proteins into microdomains is proposed to facilitate signal transduction; but constraints on microdomain size, mobility and diffusion that might realize this function are undefined. Here we interrogate a stochastic spatial model of the plasma membrane to determine how microdomains affect protein dynamics. Taking lipid rafts as a representative microdomain we show that reduced mobility in rafts, segregates dynamically partitioning proteins, but the equilibrium concentration is largely independent of raft size and mobility. Rafts weakly impede small-scale protein diffusion but more strongly impede long-range protein mobility. The long-range mobility of raft-partitioning and raft-excluded proteins however is reduced to similar extents: demonstrating that FRAP experiments may not discriminate between raft and non-raft proteins. Interestingly, specific inter-protein collision rates are maximal when rafts are small (diameter 6-14nm), mobile, present at low density and exhibit high affinity for the protein. Generalizing these results we conclude that microdomains operate as protein concentrators or isolators that act as nano-scale interaction chambers.