Predicting lipid sorting in curved membranes.

Most biological membranes are curved, and both lipids and proteins play a role in generating curvature. For any given membrane shape and composition, it is not trivial to determine whether lipids are laterally distributed in a homogeneous or inhomogeneous way, and whether the inter-leaflet distribution is symmetric or not. Here we present a simple computational tool that allows to predict the preference of any lipid type for membranes with positive vs. negative curvature, for any given value of curvature. The tool is based on molecular dynamics simulations of tubular membranes with hydrophilic pores. The pores allow spontaneous, barrierless flip-flop of most lipids, while also preventing differences in pressure between the inner and outer water compartments and minimizing membrane asymmetric stresses. Specifically, we provide scripts to build and analyze the simulations. We test the tool by performing simulations on simple binary lipid mixtures, and we show that, as expected, lipids with negative intrinsic curvature distribute to the tubule inner leaflet, the more so when the radius of the tubular membrane is small. Compared to other existing computational methods, relying on membrane buckles and tethers, our method is based on spontaneous inter-leaflet transport of lipids, and therefore allows to explore lipid distribution in asymmetric membranes. The method can easily be adapted to work with any molecular dynamics code and any force field.

The interaction of steroids with phospholipid bilayers and membranes.

Steroids are critical for various physiological processes and used to treat inflammatory conditions. Steroids act by two distinct pathways. The genomic pathway is initiated by the steroid binding to nuclear receptors while the non-genomic pathway involves plasma membrane receptors. It has been proposed that steroids might also act in a more indirect mechanism by altering biophysical properties of membranes. Yet, little is known about the effect of steroids on membranes, and steroid-membrane interactions are complex and challenging to characterise. The focus of this review is to outline what is currently known about the interactions of steroids with phospholipid bilayers and illustrate the complexity of these systems using cortisone and progesterone as the main examples. The combined findings from current work demonstrate that the hydrophobicity and planarity of the steroid core does not provide a consensus for steroid-membrane interactions. Even small differences in the substituents on the steroid core can result in significant changes in steroid-membrane interactions. Furthermore, steroid-induced changes in phospholipid bilayer properties are often dependent on steroid concentration and lipid composition. This complexity means that currently there is insufficient information to establish a reliable structure-activity relationship to describe the effect of steroids on membrane properties. Future work should address the challenge of connecting the findings from studying the effect of steroids on phospholipid bilayers to cell membranes. Insights from steroid-membrane interactions will benefit our understanding of normal physiology and assist drug development.