(380c) Increased H-Bonding in Dppe Versus DPPC Headgroups Leads to Substantial Interfacial Rheological Differences in Dppe- & DPPC-Cholesterol Monolayers | AIChE

(380c) Increased H-Bonding in Dppe Versus DPPC Headgroups Leads to Substantial Interfacial Rheological Differences in Dppe- & DPPC-Cholesterol Monolayers


White, A. - Presenter, University of California, Riverside
Ghate, P., University of California, Riverside
Onyeagoro, C., University of California, Riverside
Min, Y., University Of California Riverside
Lipids are primary building blocks of biological membranes, and they come in many varieties. Glycerophospholipids are particularly important for membrane structure and function, and within this class phosphatidylcholines (PC) and phosphatidylethanolamines (PE) are the two most abundant lipids in mammalian cells. Together with similarly abundant lipids such as cholesterol (CHOL), these lipids undergo complicated intermolecular interactions that define the membrane, for example forming microdomains or “lipid rafts” that play important functions in cell signaling and adsorption of specific proteins, membrane stability, and changes in mechanical properties. It has been demonstrated that subtle changes in the lipid composition can have major implications in the function and structure of varied biological membranes from cancer cell walls to the myelin sheath.

PC and PE lipids are defined by their respective head groups, and they can contain many different combinations of two fatty acyl tails with varying chain length and saturation. Both PC and PE head groups are zwitterionic, but PE can be both a hydrogen bond acceptor and donor while PC can only be an acceptor. This difference allows for increased hydration of PE versus PC and additionally leads to stronger inter-head group hydrogen bonding between PE lipids. While comparisons of PE and PC lipid monolayer formation and rheology have been performed, we are unaware of studies investigating the effect of PE versus PC lipids in combination with CHOL on film thermodynamics and rheology.

In this presentation we explore the consequences of the PE versus PC headgroup in the formation and interfacial rheology of binary phospholipid-CHOL monolayers. For this purpose, we choose 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) which both have the same symmetric C16:0 fatty acyl tails. Using the pendant drop technique, we perform both surface pressure versus area isotherms and oscillating pendant drop rheology on DPPC-CHOL and DPPE-CHOL films with varying CHOL content.

We demonstrate that while CHOL induces well-known condensation in DPPC monolayers, CHOL causes more complicated behavior in DPPE monolayers, including monolayer condensation at low CHOL content and expansion at high CHOL content. Through a thermodynamic analysis, we quantify this effect by calculating the excess Gibbs free energy of mixing during monolayer compression, where DPPE-CHOL monolayers transition from negative (net attraction between DPPE and CHOL) to positive (net repulsion between DPPE and CHOL) values as CHOL content is increased. This supports the interpretation that stronger inter-head group hydrogen bonding between DPPE lipids favors immiscibility at high CHOL concentrations in contrast to DPPC-CHOL films.

The thermodynamic analysis is used to further interpret differences in interfacial rheology. Due to the increased hydration and penetration into the aqueous phase, DPPE in the absence of CHOL forms less cohesive monolayers and results in lower dilatational moduli (softer films) than DPPC. However, the addition of CHOL causes DPPE-CHOL films to become stiffer than DPPC-CHOL. We hypothesize that this reversal in behavior is due to the combined effects of dehydration induced by the presence of CHOL coupled with stronger DPPE-DPPE interactions. Our results simultaneously improve our understanding of complicated relationships between lipids in biological films while highlighting the complexity and questions yet to be addressed in the role of lipid composition on biological membrane properties.