Dynamic Water Hydrogen-Bond Networks at the Interface of a Lipid Membrane Containing Palmitoyl-Oleoyl Phosphatidylglycerol

Abstract

Lipid membrane interfaces are complex environments that host essential cellular processes such as binding of proteins or drug molecules. A key open question is how water molecules at the interface of membranes with anionic lipids participate in protein binding. To address this question, we studied the dynamics of water hydrogen bonding at the interface of membranes composed of phosphatidylcholine and phosphatidylglycerol, and implemented an algorithm to identify hydrogen-bonded networks at the interface of a lipid membrane, and to characterize their dynamics and linear connections. We find that the membrane interface is characterized by a rich network of hydrogen-bonded water chains that bridge lipid headgroups, some of which form transient lipid clusters. Water-mediated bridges between with lipid phosphate groups are dynamic, with residence lifetimes on the order of picoseconds. These clusters of water/lipid headgroup hydrogen bonds could provide a platform for the binding of proteins or of drug molecules with cationic groups.

Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology

“…Such interactions are also mediated by water (Karathanou and Bondar 2018), salts (Friedman 2018; Pineda De Castro et al. 2016a), and other solutes, including drug molecules (Karlsson et al.…”

“…A key open question here is how cations and positively charged protein regions might bind at the hydrated lipid membrane interface. Atomistic simulations of lipid membranes composed of mixtures of phosphatidylcholine and phosphatidylglycerol lipids (4:1 and 5:1 POPC and POPG) were used to derive a molecular picture of the complex dynamics at the interface of these membranes (Karathanou and Bondar 2018). …”

“…7Hydrogen-bonding water bridges between lipid phosphate groups. The data are from a simulation of a membrane composed of 4:1 POPC/POPG lipids (Karathanou and Bondar 2018). a Illustration of the algorithm used to identify unique water bridges of the shortest distance between two lipid phosphate groups; green lines indicate the shortest hydrogen bond network found for the configuration used.…”

“…During the dynamics, most paths have lengths of 1 or 2, with a significantly smaller probability for the longer linear paths (). The two membrane systems studied had similar dynamics of the water hydrogen bond networks (Karathanou and Bondar 2018). …”

Lipid Membranes and Reactions at Lipid Interfaces: Theory, Experiments, and Applications

“…Karathanou and Bondar (2018) present an algorithm for identifying water/phosphate hydrogen-bond networks at the lipid headgroup interface, and for characterizing the dynamics of hydrogen-bonded lipid phosphate clusters. Linear clusters of lipid phosphates bridged by a hydrogen-bonded water molecule can extend to transiently bridge up to six lipid molecules.…”