Model Plasma Membrane exhibits a Microemulsion in both Leaves providing a Foundation for “Rafts”

Abstract

We consider a model plasma membrane, one that describes the outer leaf as consisting of sphingomyelin, phosphatidylcholine, and cholesterol, and the inner leaf of phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, and cholesterol. Their relative compositions are taken from experiment, and the cholesterol freely interchanges between leaves. Fluctuations in composition are coupled to fluctuations in the membrane height as in the Leibler-Andelman mechanism. Provided that the membrane is of relatively constant thickness, this coupling of fluctuations also provides a coupling between the composition fluctuations of the two leaves. Structure functions display, for components in both leaves, a peak at non-zero wavevector. This indicates that the disordered fluid membrane is characterized by structure on a scale given by membrane properties. From measurements on the plasma membrane, this scale is on the order of 100 nm. The theory provides a tenable basis for the origin of "rafts". Statement of SignificanceThe hypothesis that the plasma membrane is not homogeneous, but rather is heterogeneous, with rafts" of one composition floating in a sea of another, has overturned conventional views of this membrane and how it functions. Proteins prefer either the raft or the sea, and so are not uniformly distributed. Hence they perform more efficiently. From experiment, rafts are thought to be about 100 nm. However there is no realistic model that provides: a length scale for the rafts; a raft in both leaves of the membrane; the composition of the raft. We provide such a model. In contrast to other theories, the raft and sea are distinguished not only by composition, but also by a difference in curvature.

Recent Experiments Support a Microemulsion Origin of Plasma Membrane Domains: Dependence of Domain Size on Physical Parameters

“…Because the most numerous lipids in the outer leaf are SM, POPC, and cholesterol [ 25 ], one should characterize this leaf by at least three order parameters, the local mol fractions of the three species. We have done this elsewhere [ 11 ]. Of these three, only two are independent, as the sum of the three local mol fractions is unity.…”

“…The major components of the inner leaf of the plasma membrane are palmitoyloleoyl-phosphatidylserine, (POPS), palmitoyloleoyl-phosphatidylethanolamine (POPE), POPC, and cholesterol [ 25 ]. Consequently, one should describe this leaf by at least three independent order parameters, as in our previous work [ 11 ]. Again for simplicity, we describe this leaf by a single order parameter, which represents the local difference between the sum of the mol fractions of POPC and POPS and that of the sum of POPE and cholesterol.…”

“…Again for simplicity, we describe this leaf by a single order parameter, which represents the local difference between the sum of the mol fractions of POPC and POPS and that of the sum of POPE and cholesterol. This choice was motivated by our recent work [ 11 ]. We further simplify by considering only the local average of these order parameters: .…”

“…The other is rich in the low-melting-temperature lipid, and is denoted "liquid disordered" (ld) [ 8 ]. We have argued [ 9 , 10 , 11 ] that the idea that nanoscopic domains are coexisting liquid phases is an untenable one for several reasons. First it provides no explanation for the nanometer domain size; domains of two coexisting phases are of the size of the system itself, i.e., macroscopic.…”

“…An alternative explanation for the origins of the “rafts” and “sea” is that they result from a microemulsion of regions having liquid-ordered-like and liquid-disordered-like properties [ 9 , 10 , 11 ]. It is useful to recall that in a bulk system that can exhibit phase separation, its components can be emulsified by the addition of a surfactant, a molecule that essentially drives the surface tension between the phases to zero.…”