Nonideal mixing of phosphatidylserine and phosphatidylcholine in the fluid lamellar phase

Huang, Juyang; Swanson, Joy E.; Dibble, Andrew R. G.; Hinderliter, Anne; Feigenson, Gerald W.

doi:10.1016/s0006-3495(93)81382-1

Cited by 82 publications

(69 citation statements)

References 42 publications

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“…4) which all of the acyl chains in both phospholipids were either saturated or unsaturated. The origin of this difference is unclear, but it is known that in PC-PS membranes where each lipid has different acyl chains, the lipid mixing is nonideal (82) and the PS has a higher thermodynamic activity (83). In contrast, mNG-MARCKS and mNG-(Ev2) 2 had different membrane binding properties than RSV MA, Gag, and mNG-KR8 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Effects of Membrane Charge and Order on Membrane Binding of the Retroviral Structural Protein Gag

Wen

Dick

Feigenson

et al. 2016

J Virol

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The retroviral structural protein Gag binds to the inner leaflet of the plasma membrane (PM), and many cellular proteins do so as well. We used Rous sarcoma virus (RSV) Gag together with membrane sensors to study the principles governing peripheral protein membrane binding, including electrostatics, specific recognition of phospholipid headgroups, sensitivity to phospholipid acyl chain compositions, preference for membrane order, and protein multimerization. We used an in vitro liposome-pelleting assay to test protein membrane binding properties of Gag, the well-characterized MARCKS peptide, a series of fluorescent electrostatic sensor proteins (mNG-KRn), and the specific phosphatidylserine (PS) binding protein Evectin2. RSV Gag and mNG-KRn bound well to membranes with saturated and unsaturated acyl chains, whereas the MARCKS peptide and Evectin2 preferentially bound to membranes with unsaturated acyl chains. To further discriminate whether the primary driving force for Gag membrane binding is electrostatic interactions or preference for membrane order, we measured protein binding to giant unilamellar vesicles (GUVs) containing the same PS concentration in both disordered (Ld) and ordered (Lo) phases. RSV Gag and mNG-KRn membrane association followed membrane charge, independent of membrane order. Consistent with pelleting data, the MARCKS peptide showed preference for the Ld domain. Surprisingly, the PS sensor Evectin2 bound to the PS-rich Ld domain with 10-fold greater affinity than to the PS-rich Lo domain. In summary, we found that RSV Gag shows no preference for membrane order, while proteins with reported membrane-penetrating domains show preference for disordered membranes. IMPORTANCERetroviral particles assemble on the PM and bud from infected cells. Our understanding of how Gag interacts with the PM and how different membrane properties contribute to overall Gag assembly is incomplete. This study examined how membrane charge and membrane order influence Gag membrane association. Consistent with previous work on RSV Gag, we report here that electrostatic interactions provide the primary driving force for RSV Gag membrane association. Using phase-separated GUVs with known lipid composition of the Ld and Lo phases, we demonstrate for the first time that RSV Gag is sensitive to membrane charge but not membrane order. In contrast, the cellular protein domain MARCKS and the PS sensor Evectin2 show preference for disordered membranes. We also demonstrate how to define GUV phase composition, which could serve as a tool in future studies of protein membrane interactions.T he retroviral structural protein Gag provides the primary driving force for virus assembly at the inner leaflet of the plasma membrane (PM), and Gag alone is sufficient to assemble into virus-like particles (VLPs) in cells (1) and also in vitro (2). Gag is synthesized in the cytosol and then is targeted to the PM by the N-terminal domain, MA. How Gag interacts with the inner leaflet of the PM and how the biophysical properties of the PM...

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Section: Resultsmentioning

confidence: 99%

Effects of Membrane Charge and Order on Membrane Binding of the Retroviral Structural Protein Gag

Wen

Dick

Feigenson

et al. 2016

J Virol

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“…[see e.g. 24, 1, 58] The principal reason for this is the “diffusion problem”. Diffusion of lipids or cholesterol in bilayers is simply too slow ( D ≈ 10 −12 m 2 / s ) which means that the times needed for significant lateral displacement of lipids in a membrane should be in the tens of microseconds to millisecond range, three or more orders of magnitude longer than most current atomistic MD simulations.…”

Section: Introductionmentioning

confidence: 99%

Multiscale simulations of heterogeneous model membranes

Pandit

Scott

2009

Biochimica et Biophysica Acta (BBA) - Biomembranes

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This review will focus on computer modeling aimed at providing insights into the existence, structure, size, and thermodynamic stability of localized domains in membranes of heterogeneous composition. Modeling the lateral organization within a membrane is problematic due to the relatively slow lateral diffusion rate for lipid molecules so that microsecond or longer time scales are needed to fully model the formation and stability of a raft in a membrane. Although atomistic simulations currently are not able to reach this scale, they can provide data on the intermolecular forces and correlations that are involved in lateral organization. These data can be used to define coarse grained models that are capable of predictions of lateral organization in membranes. In this paper, we review modeling efforts that use interaction data from MD simulations to construct coarse grained models for heterogeneous bilayers. In this review we will discuss MD simulations done with the aim of gaining the information needed to build accurate coarse-grained models. We will then review some of the coarse-graining work, emphasizing modeling that has resulted from or has a basis in atomistic simulations.

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“…From the microscopy pictures we characterized the vesicle morphologies and measured the corresponding dimensions using a graduated reticule of 2 microns/division. Note that above the concentration range 2-8 mM there is non-ideal mixing of PC and PS [2]. Thus, our samples are prepared below this range, i.e.…”

Section: Resultsmentioning

confidence: 99%

Shapes of Mixed Phospholipid Vesicles

2006

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Abstract. We studied the shape of phospholipid vesicles prepared by hydration of a mixture of phosphatidylcholine (SOPC) and phosphatidylserine (SOPS) in different proportions. The aim of the work is to obtain some insight into the influence of the chemical composition of a biomembrane on its shape. The optical microscopy results show that the shape of the vesicles depend on the SOPC:SOPS composition. For low SOPS contents, coiled cylindrical vesicles are observed. The results suggest that specific compositions of the SOPC:SOPS vesicles produce some spontaneous curvature on the membrane and then a coiling instability.

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Nonideal mixing of phosphatidylserine and phosphatidylcholine in the fluid lamellar phase

Cited by 82 publications

References 42 publications

Effects of Membrane Charge and Order on Membrane Binding of the Retroviral Structural Protein Gag

Effects of Membrane Charge and Order on Membrane Binding of the Retroviral Structural Protein Gag

Multiscale simulations of heterogeneous model membranes

Shapes of Mixed Phospholipid Vesicles

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