In addition to obtaining the highly precise volumes of lipids in lipid bilayers, it has been desirable to obtain the volumes of parts of each lipid, such as the methylenes and terminal methyls on the hydrocarbon chains and the headgroup. Obtaining such component volumes from experiment and from simulations is re-examined, first by distinguishing methods based on apparent versus partial molar volumes. While somewhat different, both these methods give results that are counterintuitive and that differ from results obtained by a more local method that can only be applied to simulations. These comparisons reveal differences in the average methylene component volume that result in larger differences in the headgroup component volumes. Literature experimental volume data for unsaturated phosphocholines and for alkanes have been used and new data have been acquired for saturated phosphocholines. Data and simulations cover extended ranges of temperature to assess both the temperature and chain length dependence of the component volumes. A new method to refine the determination of component volumes is proposed that uses experimental data for different chain lengths at temperatures guided by the temperature dependence determined in simulations. These refinements enable more precise comparisons of the component volumes of different lipids and alkanes in different phases. Finally, the notion of free volume is extended to components using the Lennard-Jones radii to estimate the excluded volume of each component. This analysis reveals that head group free volumes are relatively independent of thermodynamic phase, while both the methylene and methyl free volumes increase dramatically when bilayers transition from gel to fluid.

cyclodepsipeptide ring orientation. In summary, almost half of the side chains in teixobactin participate in membrane-anchoring and not direct lipid II-binding. These hydrophobic residues appear invariable in several studies of the structure-activity relationship of teixobactin derivatives, suggesting that membrane binding and insertion act as an essential step in its antibacterial mechanism. Phenol-soluble modulin a3 (PSMa3) is a cytotoxic peptide secreted by Staphylococcus aureus. Increased expression of PSMa3 is associated with the enhanced toxicity of community-associated Methicillin-resistant S. aureus (CA-MRSA), a highly virulent strain of MRSA. Though previous reports suggest membrane disruption, the mechanism of PSMa3mediated cell death is not fully understood. Here, we used a stereochemical strategy to examine the mechanism of cytotoxicity. We found that racemic PSMa3 (L and D-PSMa3 mixed at 1:1 ratio) can form non-toxic and stable fibrils, while chiral PSMa3 remains toxic under the same conditions. We solved the crystal structure of racemic PSMa3 at 1.4Å , which shows a cross-a, homo-chiral packing pattern along the crystal growth axis. We conclude that PSMa3 exerts toxicity primarily through interactions with the lipid bilayer of a cell, and that fibril formation is not necessary for cytotoxicity.