Measuring the mechanical properties of asymmetric membranes in computer simulations -- new methods and insights

Abstract: We present Monte Carlo simulations of an ultra coarse-grained lipid bilayer with different number of lipids on both leaflets. In the simulations, we employ a new method for measuring the elastic parameters of the membrane, including the area per lipid, area elasticity modulus, and bending rigidity. The method also allows to measure the spontaneous curvature and non-local bending modulus, which are not accessible by standard computer simulations with periodic boundary conditions. For membranes with lipid densities much smaller than the liquid to gel transition density, $\rho_g$, we find a very good agreement between the simulation results and the theory expressing the bilayer elastic free energy as the sum of quadratic free energies in the strains associated with the area density and the local curvature of the monolayers. The theory fails when the lipid area density (in the symmetric reference case) is only slightly smaller than $\rho_g$. Increasing the degree of asymmetry and changing the density of the condensed leaflet to a value larger than $\rho_g$, causes the layer to phase separate between regions with distinct densities which, in turn, may also induce density variations in the dilated liquid layer. Moreover, the phase separation may also trigger local curvature variations along the membrane, which can be attributed to the disparity between the values of the elastic parameters of the coexisting bilayer segments that are mechanically coupled. This mechanism leading to density-curvature variations and instabilities may play a role in cellular processes occurring in liquid-ordered raft domains that are surrounded by the disordered liquid matrix of the cell.