Computing Individual Area per Head Group Reveals Lipid Bilayer Dynamics

Lipid bilayers express a range of phases from solid-like to gel-like to liquid-like as a function of temperature and lipid surface concentration. The area occupied per lipid head group serves as one useful indicator of the bilayer phase, in conjunction with the two-dimensional radial distribution function (i.e., structure factor) within the bilayer. Typically, the area per head group is determined by dividing the bilayer area equally among all head groups. Such an approach is less satisfactory for a multicomponent set of diverse lipids. In this work, area determination is performed on a lipid-by-lipid basis by attributing to a lipid the volume that surrounds each atom. Voronoi tessellation provides this division of the interfacial region on a per-atom basis. The method is applied to a multicomponent system of water, NaCl, and 19 phospholipid types that was devised recently [Langmuir2022, 38, 9481-9499] as a computational representation of the Gram-positive Staphylococcus aureus phospholipid bilayer. Results demonstrate that lipids and water molecules occupy similar extents of area within the interfacial region; ascribing area only to head groups implicitly incorporates assumptions about head group hydration. Results further show that lipid tails provide non-negligible contributions to area on the membrane side of the bilayer-water interface. Results for minimum and maximum area of individual lipids reveal that spontaneous fluctuations displace head groups more than 10 Å from the interfacial region during an NPT simulation at 310 K, leading to a zero contribution to total area at some times. Total area fluctuations and fluctuations per individual lipid relax with a correlation time of ∼10 ns. The method complements density profile as an approach to quantify the structure and dynamics of computational lipid bilayers.