Structure of lateral heterogeneities in a coarse-grained model for multicomponent membranes.

We study the lateral domain structure in a coarse-grained molecular model for multicomponent lipid bilayers by semi-grandcanonical Monte Carlo simulations. The membranes are filled with liquid ordered (lo) domains surrounded by a liquid disordered (ld) matrix. Depending on the membrane composition and temperature, we identify different morphological regimes: one regime (I) where the lo domains are small and relatively compact, and two regimes (II, II') where they are larger and often interconnected. In the latter two regimes, the ld matrix forms a network of disordered trenches separating the lo domains, with a relatively high content of interdigitated line defects. Since such defects are also a structural element of the modulated ripple phase in one component membranes, we argue that the regimes II, II' may be amorphous equivalents of the ripple phase in multicomponent membranes. We also analyze the local structure and provide evidence that the domains in regime I are stabilized by a monolayer curvature mechanism postulated in earlier work [S. Meinhardt et al., PNAS, 2013, 110, 4476].

Monolayer curvature stabilizes nanoscale raft domains in mixed lipid bilayers.

According to the lipid raft hypothesis, biological lipid membranes are laterally heterogeneous and filled with nanoscale ordered "raft" domains, which are believed to play an important role for the organization of proteins in membranes. However, the mechanisms stabilizing such small rafts are not clear, and even their existence is sometimes questioned. Here, we report the observation of raft-like structures in a coarse-grained molecular model for multicomponent lipid bilayers. On small scales, our membranes demix into a liquid ordered (lo) phase and a liquid disordered (ld) phase. On large scales, phase separation is suppressed and gives way to a microemulsion-type state that contains nanometer-sized lo domains in an ld environment. Furthermore, we introduce a mechanism that generates rafts of finite size by a coupling between monolayer curvature and local composition. We show that mismatch between the spontaneous curvatures of monolayers in the lo and ld phases induces elastic interactions, which reduce the line tension between the lo and ld phases and can stabilize raft domains with a characteristic size of the order of a few nanometers. Our findings suggest that rafts in multicomponent bilayers might be closely related to the modulated ripple phase in one-component bilayers.

Structure of Cholesterol in Lipid Rafts.

Rafts, or functional domains, are transient nano-or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking, and lipid or protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules, we observe raftlike structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to ordering of the cholesterol molecules in the raftlike structures were observed and indexed by two different structures: a monoclinic structure of ordered cholesterol pairs of alternating direction in equilibrium with cholesterol plaques, i.e., triclinic cholesterol bilayers.

Separation of chiral particles in micro- or nanofluidic channels.

We propose a method to separate enantiomers in microfluidic or nanofluidic channels. It requires flow profiles that break chiral symmetry and have regions with high local shear. Such profiles can be generated in channels confined by walls with different hydrodynamic boundary conditions (e.g., slip lengths). Because of a nonlinear hydrodynamic effect, particles with different chirality migrate at different speeds and can be separated. The mechanism is demonstrated by computer simulations. We investigate the influence of thermal fluctuations (i.e., the Péclet number) and show that the effect disappears in the linear response regime. The details of the microscopic flow are important and determine which volume forces are necessary to achieve separation.