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Fluid Phase Coexistence in Biological Membrane: Insights from Local Nonaffine Deformation of Lipids.

ABSTRACT: Lateral heterogeneities in biomembranes play a crucial role in various physiological functions of the cell. Such heterogeneities lead to demixing of lipid constituents and formation of distinct liquid domains in the membrane. We study lateral heterogeneities in terms of topological rearrangements of lipids to identify the liquid-liquid phase coexistence in model membranes. Using ideas from the physics of amorphous systems and glasses, we calculate the degree of nonaffine deformation associated with individual lipids to characterize the liquid-ordered (L_o) and liquid-disordered (L_d) regions in model lipid bilayers. We explore the usage of this method on all-atom and coarse-grained lipid bilayer trajectories. This method is helpful in defining the instantaneous L_o-L_d domain boundaries in complex multicomponent bilayer systems. The characterization is also used to highlight the effect of line-active molecules on the phase boundaries and domain mixing. Overall, we propose a framework to explore the molecular origin of spatial and dynamical heterogeneity in biomembrane systems, which can be exploited not only in computer simulations but also in experiments.

SUBMITTER: Iyer SS

PROVIDER: S-EPMC6035292 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Fluid Phase Coexistence in Biological Membrane: Insights from Local Nonaffine Deformation of Lipids.

Iyer Sahithya S SS Tripathy Madhusmita M Srivastava Anand A

Biophysical journal 20180701 1

Lateral heterogeneities in biomembranes play a crucial role in various physiological functions of the cell. Such heterogeneities lead to demixing of lipid constituents and formation of distinct liquid domains in the membrane. We study lateral heterogeneities in terms of topological rearrangements of lipids to identify the liquid-liquid phase coexistence in model membranes. Using ideas from the physics of amorphous systems and glasses, we calculate the degree of nonaffine deformation associated w ...[more]

PMID: 29972803

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Project description:Phospholipids are important to cellular function and are a vital structural component of plasma and organelle membranes. These membranes isolate the cell from its environment, allow regulation of the internal concentrations of ions and small molecules, and host diverse types of membrane proteins. It remains extremely challenging to identify specific membrane protein-lipid interactions and their relative strengths. Native mass spectrometry, an intrinsically gas-phase method, has recently been demonstrated as a promising tool for identifying endogenous protein-lipid interactions. However, to what extent the identified interactions reflect solution- versus gas-phase binding strengths is not known. Here, the "Extended" Kinetic Method and ab initio computations at three different levels of theory are used to experimentally and theoretically determine intrinsic gas-phase basicities (GB, ΔG for deprotonation of the protonated base) and proton affinities (PA, ΔH for deprotonation of the protonated base) of six lipids representing common phospholipid types. Gas-phase acidities (ΔG and ΔH for deprotonation) of neutral phospholipids are also evaluated computationally and ranked experimentally. Intriguingly, it is found that two of these phospholipids, sphingomyelin and phosphatidylcholine, have the highest GB of any small, monomeric biomolecules measured to date and are more basic than arginine. Phosphatidylethanolamine and phosphatidylserine are found to be similar in GB to basic amino acids lysine and histidine, and phosphatidic acid and phosphatidylglycerol are the least basic of the six lipid types studied, though still more basic than alanine. Kinetic Method experiments and theory show that the gas-phase acidities of these phospholipids are high but less extreme than their GB values, with phosphatidylserine and phosphatidylglycerol being the most acidic. These results indicate that sphingomyelin and phosphatidylcholine lipids can act as charge-reducing agents when dissociated from native membrane protein-lipid complexes in the gas phase and provide a straightforward model to explain the results of several recent native mass spectrometry studies of protein-lipid complexes.

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Fluid Phase Coexistence in Biological Membrane: Insights from Local Nonaffine Deformation of Lipids.

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Fluid Phase Coexistence in Biological Membrane: Insights from Local Nonaffine Deformation of Lipids.

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