3D Packing Defects in Lipid Membrane as a Function of Membrane Order

Lipid membrane packing defects are considered as essential parameter that regulates specific membrane binding of several peripheral proteins. In absence of direct experimental characterization, lipid packing defects and their role in the binding of peripheral proteins are generally investigated through computational studies, which have been immensely successful in unraveling the key steps of the membrane-binding process. However, packing defects are calculated using 2-dimensional projections and the crucial information on their depths is generally overlooked. Here we present a simple yet computationally efficient algorithm, which identifies these defects in 3-dimensions. We employ the algorithm to understand the nature of packing defects in flat bilayer membranes exhibiting liquid-ordered ( L o ), liquid-disordered ( L d ) and co-existing L o / L d phases. Our results indicate the presence of shallower and smaller defects in the L o phase membranes as compared to the defects in L d and mixed L o / L d phase membranes. Such analyses can elucidate the molecular scale mechanisms that drive the preferential localization of certain proteins to either of the liquid phases or their interface. Moreover, on the methodology front, our analyses suggest that the projection based 2-dimensional calculation of packing defects might result in inaccurate quantification of their sizes - a very important feature for membrane association of protein motifs, thus advocating the importance of the 3-dimensional calculations.