Graph-Based Analyses of Dynamic Water-Mediated Hydrogen-Bond Networks in Phosphatidylserine: Cholesterol Membranes

Phosphatidylserine lipids are anionic molecules present in eukaryotic plasma membranes, where they have essential physiological roles. The altered distribution of phosphatidylserine in cells such as apoptotic cancer cells, which, unlike healthy cells, expose phosphatidylserine, is of direct interest for the development of biomarkers. We present here applications of a recently implemented Depth-First-Search graph algorithm to dissect the dynamics of transient water-mediated lipid clusters at the interface of a model bilayer composed of 1-palmytoyl-2-oleoyl-sn-glycero-2phosphatidylserine (POPS) and cholesterol. Relative to a reference POPS bilayer without cholesterol, in the POPS:cholesterol bilayer there is a somewhat less frequent sampling of relatively complex and extended water-mediated hydrogen-bond networks of POPS headgroups. The analysis protocol used here is more generally applicable to other lipid:cholesterol bilayers.

Automated summary

Phosphatidylserine lipids, anionic molecules found in eukaryotic plasma membranes, play essential roles in cellular physiology. Understanding the altered distribution of phosphatidylserine, particularly in apoptotic cancer cells, has important implications for biomarker development. This study utilizes a graph algorithm to study the dynamics of water-mediated lipid clusters at the interface of a model bilayer, providing insights into the behavior of phosphatidylserine in the presence of cholesterol.