  Membrane organization is essential for cellular functions such as signal
transduction and membrane trafficking. A major challenge is to understand the
lateral heterogeneous structures in membranes and membrane fluidity in the
presence of inclusions. Based on a considerable amount of experimental evidence
for lateral organization of lipid membranes which share astonishingly similar
features in the presence of different inclusions, we first present a general
model system of bilayer membranes embedded by nanosized inclusions, and explain
experimental findings. Here, the hydrophobic inclusions are simple models of
intrinsic membrane proteins, cholesterol embedded in the membrane, hydrophobic
drugs, or other nanoparticles for bio-medical applications. It is found that
lipid/inclusion-rich raft domains are formed at moderate inclusion
concentrations, and disappear with the increase of inclusions. At high
inclusion content, chaining of inclusions occurs due to the effective
attraction between inclusions mediated by lipids. Meanwhile, increasing
inclusions can also cause thickening of the membrane, and the distribution of
inclusions undergoes a layering transition from one-layer located in the
bilayer midplane to two-layer structure arranged into the two leaflets of a
bilayer. Our theoretical predictions address the complex interactions between
membranes and inclusions, suggesting a unifying mechanism which reflects the
competition between the conformational entropy of lipids favoring the formation
of lipid-rich rafts and the steric repulsion of inclusions leading to the
uniform dispersion.
