Identifying Lipid Membrane Packing Defects in 3-Dimension: When Depth Does Matter

Abstract

Being extremely difficult to characterize experimentally, lipid membrane packing defects and their role in the binding of peripheral proteins are generally investigated in computational studies. Such studies, while have been immensely successful in unraveling the key steps of the binding process, analyze the packing defects using their 2-dimensional projection, thus ignoring the crucial information on their depths. Here we present a simple yet computationally efficient algorithm, which identifies these defects in 3-dimension. We employ the algorithm to understand the nature of packing defects in flat bilayer membranes exhibiting liquid-ordered (Lo) and liquid-disordered (Ld) phases. Our results indicate the presence of shallower and smaller defects in the Lo phase membranes as compared to the Ld and mixed ones, in accordance to their distinct topological arrangements and temporal evolutions. Such analyses can elucidate the molecular scale picture behind the preferential binding 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, thus advocating the importance of the 3-dimensional calculation.