Identifying systematic errors in a power spectral analysis of simulated lipid membranes.

The elastic properties of lipid membranes can be measured by monitoring their thermal fluctuations. For instance, comparing the power spectra of membrane shape or lipid director fluctuations with predictions based on suitable continuum theories gives access to bending-, tilt-, and twist-moduli. However, to do so in a computer simulation, we must first define a continuum surface shape and lipid director field from the discrete configurations of lipid molecules in a typically fairly small box. Here, we show that the required mapping choices, as well as the details of the subsequent data analysis, can shift the measured values of these moduli by far more than their statistical uncertainties. We investigate the resulting systematic errors on the basis of atomistic simulation trajectories for 13 different lipids, previously published by Venable et al. [Chem. Phys. Lipids 192, 60-74 (2015)]. Specifically, we examine mapping choices for surface- and tilt-field definitions, normalizing and averaging lipid directors, accounting for wave vector dependent time autocorrelations, error propagation, and finding the right fitting range. We propose a set of criteria that may help to decide upon a particular combination of choices underlying the fluctuation analysis, and we make several recommendations based on these. While systematic shifts in observables that are extracted from large-wavelength limits vanish, in principle, for sufficiently large system size, no such exact limit exists for intrinsically local parameters, such as the twist modulus or the splay-tilt coupling, and so not all potential choices can be trivially verified.

A consistent quadratic curvature-tilt theory for fluid lipid membranes.

The tilt of a lipid molecule describes the deviation of its orientation away from the local normal of its embedding membrane. Tilt is the subleading degree of freedom after a membrane's geometry, and it becomes relevant at scales comparable to lipid bilayer thickness. Building on earlier work by Hamm and Kozlov [Eur. Phys. J. E 3, 323 (2000)], who envisioned lipid membranes as thin prestressed fluid elastic films, and Terzi and Deserno [J. Chem. Phys. 147, 084702 (2017)], who discovered a new coupling term between splay and tilt divergence, we construct a theory of membrane elasticity that is quadratic in geometry and tilt and complete at order 1/length2. We show that a general and consistent treatment of both lateral and transverse depth-dependent shear stresses creates several contributions to the elastic energy density, of which only a subset had previously been identified. Apart from the well-known penalty of lipid twist (the curl of tilt), these terms generate no qualitatively new phenomenology, but they quantitatively revise the connections between the moduli of a tilt-curvature theory and its underlying microscopic foundation. In particular, we argue that the monolayer Gaussian curvature modulus κ¯m, widely believed to be equal to the second moment of the transmonolayer stress profile, acquires a second contribution from lipid twist, which is always negative. This could resolve the long-standing conundrum that many measured values of κ¯m appeared to have a sign that violates basic stability considerations. We also show that the previously discovered novel coupling between splay and tilt divergence is not simply proportional to κ¯m but acquires its own splay-tilt coupling modulus, κst,m. We explore the predictions of our theory for various elastic moduli and their mutual interrelations and use an extensive set of existing atomistic molecular dynamics simulations for 12 different lipid types to collectively reason about such predictions. We find that bending rigidities are captured fairly well by existing theories, while reliable predictions for local moduli, especially the splay-tilt coupling modulus, remain challenging.