Lipid Chain Upturns and Orientational Potential in Membrane Liquid Crystals

Abstract

Lipid bilayers in the fluid state are characterized by significant disorder of the acyl chains. Experimentally this can be seen by the low order parameters measured by 2H NMR spectroscopy [1, 2] and by other methods such as x-ray scattering that measures a reduced membrane thickness compared to ordered phases. In addition, IR and EPR spectroscopy that each measure a characteristic order parameter. All-atom Molecular Dynamics (MD) simulations of lipid bilayers show that acyl chain disorder can be described analytically using a mean-field orientational potential (potential of mean-torque) acting at the level of carbon segments [3]. The simplest approximation is a first-order term in which the alignment potential is quantified by a ε1 that we call a torque-strength. As shown by us and others, this approximation is sufficient for the calculation of geometric quantities such as the membrane thickness and cross-sectional area per lipid. However, there are other physical parameters of interest in the biophysics of membranes. One important parameter that contributes to the membrane free energy is the orientational entropy. Here we show that the first order mean-torque approximation needs to include an extra term (with an additional parameter ε1′) to account for chain upturns. We find that upturned carbon segments experience a stronger alignment field because upturns necessarily place the remaining carbon segments higher on the membrane normal, i.e. close to the headgroups. Such statistical models of lipid membrane structure can better account for the contributions to membrane free energy that governs biological functions such as cellular signaling by ion channels. [1] J.J. Kinnun et al. (2015). Biochim. Biophys. Acta 1858, 246-259. [2] K.J. Mallikarjunaiah et al. (2019). Phys. Chem.Chem.Phys. 21, 18422-18457. [3] H.I. Petrache et al. (2000). Biophys. J. 79, 3172-3192.