Phosphatidylinositol induces fluid phase formation and packing defects in phosphatidylcholine model membranes

Abstract

Liposomes consisted of phosphatidylinositol (PI) and phosphatidylcholine (PC) have been utilized as delivery vehicle for drugs and proteins. In the present work, we studied the effect of soy PI on physical properties of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes such as phase state of lipid bilayer, lipid packing and phase properties using multiple orthogonal biophysical techniques. The 6-dodecanoyl-2-dimethylamino naphthalene (Laurdan) fluorescence studies showed that presence of PI induces the formation of fluid phases in DMPC. Differential scanning calorimetry (DSC), temperature dependent fluorescence anisotropy measurements, and generalized polarization values for Laurdan showed that the presence of as low as 10 mol% of PI induces substantial broadening and shift to lower temperature of phase transition of DMPC. The fluorescence emission intensity of DPH labeled, PI containing DMPC lipid bilayer decreased possibly due to deeper penetration of water molecules in lipid bilayer. In order to further delineate the effect of PI on the physico chemical properties of DMPC is due to either significant hydrophobic mismatch between the acyl chains of the DMPC and that of soy PI or due to the inositol head group, we systematically replaced soy PI with PC species of similar acyl chain composition (DPPC and 18:2 (Cis) PC) or with diacylglycerol (DAG) respectively. The anisotropy of PC membrane containing soy PI showed largest fluidity change compared to other compositions. The data suggests that addition of PI alters structure and dynamics of DMPC bilayer in that it promotes deeper water penetration in the bilayer, induces fluid phase characteristics and causes lipid packing defects that involve its inositol head group.

Mammalian phospholipid homeostasis: Homeoviscous adaptation deconstructed by lipidomic data driven modelling

“…Similar studies point to the 'fluidising' ability of pure DAGs being slightly inferior to mixed chain PI (soy bean (Peng et al, 2012) and pig liver (Larijani and Dufourc, 2006) sets with lowest variance across the training and test data sets appear towards the bottom left of these plots.…”

Soy Phosphatidylinositol Containing Nanoparticle Prolongs Hemostatic Activity of B-Domain Deleted Factor VIII in Hemophilia A Mice

“…Our laboratory has previously reported a phosphatidylinositol (PI) containing lipidic nanoparticle for the delivery of full‐length FVIII . This nanoparticle is highly efficient at loading FVIII and permits a deep penetration of the FVIII molecule into the lipid bilayer because of the structural packing defects introduced by PI in phosphatidylcholine membranes . The molecular topology of the PI–FVIII complex involves association of the C2 and A2 domains of FVIII .…”

“…8 This nanoparticle is highly efficient at loading FVIII and permits a deep penetration of the FVIII molecule into the lipid bilayer because of the structural packing defects introduced by PI in phosphatidylcholine membranes. 9 The molecular topology of the PI-FVIII complex involves association of the C2 and A2 domains of FVIII. 8 These domains are involved in low-density lipoprotein receptor-related protein (LRP)-mediated cellular uptake of FVIII into endocytotic clearance (CL) pathways [10][11][12] and contain several immunodominant epitopes that can contribute to inhibitor development.…”

Is phosphatidylglycerol essential for terrestrial life?

“…PG is relatively unusual amongst lipids in that it is both invariably type 0 and anionic. Other major anionic lipids, PA [27][28][29], PI [140,141], PI-4-P [142,143] and CL [104,144], can behave as type II lipids, and with the arguable exception of PI [77], typically do so under physiological conditions. Thus, the presence of PG confers a negative charge on a membrane without increasing stored curvature elastic stress.…”