Domain Formation in the Plasma Membrane: Roles of Nonequilibrium Lipid Transport and Membrane Proteins

Compositional lipid domains (“lipid rafts”) in plasma membranes are believed to be important components of many cellular processes. The mechanisms by which cells regulate the sizes and lifetimes of these spatially extended domains are poorly understood at the moment. Here we show that the competition between phase separation in an immiscible lipid system and active cellular lipid transport processes naturally leads to the formation of such domains. Furthermore, we demonstrate that local interactions with immobile membrane proteins can spatially localize the rafts and lead to further clustering.

Figure 1

Schematic presentation of the nonequilibrium lipid transport processes considered here. Both protein-facilitated flip-flop events (upper pathway) and vesicle trafficking events between the plasma membrane and internal organelles (lower pathway) lead to an effective rearrangement of the lipid composition over a scale $\sim \ell$ in the exoplasmic leaflet.

Figure 2

Snapshots of domain structures in steady state under recycling with recycling length $\ell =4$ (left) and $\ell =1280$ (right). Notice the presence of finite-sized lipid rafts within the liquid-disordered phase.

Figure 3

Steady-state raft size vs $H$ and $\ell$. The two frames on the right display slices through the data at fixed $H$ and $\ell$, respectively.

Figure 4

Domain size distribution for lipid raft area fraction $\varphi =1/4$ and $H=1.41$ for several values of the recycling length $\ell$. $N_A$ denotes the number of domains of size $A$. The dashed line has a slope of $-1.6$ and serves as a guide to the eye.

Figure 5

Spatial localization and aggregation of lipid rafts due to membrane proteins (indicated by white circles). Left panel: raft distribution around five randomly distributed proteins. Right panel: extended raft domain in the presence a protein cluster.