Communication between the leaflets of asymmetric membranes revealed from coarse-grain molecular dynamics simulations

Shearer, Jonathan; Khalid, Syma

doi:10.1038/s41598-018-20227-1

Cited by 27 publications

(37 citation statements)

References 44 publications

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“…Indeed, the idea of matching leaflet areas from symmetric bilayers to avoid tension in a simulated asymmetric bilayer is inherently flawed-regardless of how many lipids the two leaflets have-because their areas are always constrained to be the same by the imposed periodic boundary conditions, thus hiding any nonzero leaflet tension. Randomly choosing the number of lipids in the two leaflets (41) or making the total number of lipids in the two leaflets the same (23,24) does not guarantee a 0-LT condition. A recently described method for self-assembly of coarsegrained asymmetric bilayers that ensures 0-LT (27) is intriguing, but it uses a spontaneous self-assembly process in which control over the exact compositions of the two leaflets is limited.…”

Section: Application Of the Methods To Bilayers With Diverse Propertiesmentioning

confidence: 99%

Accurate In Silico Modeling of Asymmetric Bilayers Based on Biophysical Principles

Doktorova

Weinstein

2018

Biophysical Journal

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Technological advances in the last decade have enabled the study of ever more complex and physiologically relevant model membranes to help dispel the mystery surrounding the role of plasma membrane asymmetry in various cellular processes. The slowly accumulating body of experimental data is fueling renewed interest in and the need for computational methods to support interpretations and address a wide range of problems that are still not amenable to direct experimental study. The specific appeal of molecular dynamics simulations for this purpose lies in their ability to access information at atomic resolution, which is useful for the formulation of testable mechanistic hypotheses. But, the range of questions that can be addressed reliably with such simulations is determined by the appropriate construction and simulation of asymmetric bilayer models. One essential way to achieve this goal is to follow rigorous biophysical criteria and principles. In this context, we show that the requirement for a robust comparison between the properties of simulated asymmetric and symmetric model membranes is for the tension in each bilayer leaflet to be zero. Commonly used methods for constructing asymmetric bilayers, including matching the average areas of the leaflets from the corresponding symmetric systems, do not ensure zero leaflet tension, thus precluding physically realistic changes in the areas of the two leaflets. We present, to our knowledge, a new method for identifying the ideal lipid packing in bilayers with different leaflet compositions that achieves the zero-tension goal, and discuss the basic principles underlying the biophysically correct computational study of asymmetric membranes.

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Section: Application Of the Methods To Bilayers With Diverse Propertiesmentioning

confidence: 99%

Accurate In Silico Modeling of Asymmetric Bilayers Based on Biophysical Principles

Doktorova

Weinstein

2018

Biophysical Journal

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“…Lipids in heterogeneous vesicles have been demonstrated to partition differentially between the inner and outer leaflets to minimize curvature frustration, leading to asymmetric concentrations between the leaflets 10 . While this state represents the energy minimum of the system with respect to curvature energetics, it is sometimes the case that researchers wish to simulate systems with fixed lipid ratios, for instance when the simulation attempts to reproduce an asymmetric biological membrane composition 54 . Allowing interleaflet flipflop in a heterogeneous system inevitably leads to changes to the desired leaflet compositions.…”

Section: Discussionmentioning

confidence: 99%

BUMPy: A Model-Independent Tool for Constructing Lipid Bilayers of Varying Curvature and Composition

Boyd

May

2018

J. Chem. Theory Comput.

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Molecular dynamics is a powerful tool to investigate atomistic and mesoscopic phenomenon in lipid bilayer systems. These studies have progressed with the advent of increased computational power and efforts are now increasing being directed toward investigating the role of curvature and bilayer morphology, as these are critical features of biological processes. Computational studies of lipid bilayers benefit from tools that can create starting configurations for molecular dynamics simulations, but the majority of such tools are restricted to generating flat bilayers. Generating curved bilayer configurations comes with practical complications and potential ramifications on physical properties in the simulated system if the bilayer is initiated in a high-strain state. We present a new tool for creating curved lipid bilayers that combines flexibility of shape, force field, model resolution and bilayer composition. A key aspect of our approach is the use of the monolayer pivotal plane location to accurately estimate interleaflet area differences in a curved bilayer. Our tool is named BUMPy (Building Unique Membranes in Python) is written in python, is fast and has a simple command line interface.

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“…[28][29] Despite their longer length, the LPS molecules in the OMVs achieved lateral packing comparable to the shortest LPS (Re-type) lipids found in flat E. coli outer membranes. [28][29][30] This unusually tight packing of LPS lipids can be ascribed to (i) additional fringe volume that affords LPS head groups more conformational freedom and the capacity to achieve unusually tight lamellar alignment, and (ii) compensatory lateral area expansion of neighboring phospholipids, which pushes the LPS molecules closer together than in flat membranes.…”

Section: Omvs In Watermentioning

confidence: 99%

To infect or not to infect: molecular determinants of bacterial outer membrane vesicle internalization by host membranes

Jefferies

Khalid

2019

Preprint

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Outer membrane vesicles (OMVs) are spherical liposomes that are secreted by almost all forms of Gram-negative bacteria. The nanospheres contribute to bacterial pathogenesis by trafficking molecular cargo from bacterial membranes to target cells at the host-pathogen interface. We have simulated the interaction of OMVs with host cell membranes to understand why OMV uptake depends on the length of constituent lipopolysaccharide macromolecules. Using coarse-grained molecular dynamics simulations, we show that lipopolysaccharide lipid length affects OMV shape at the host-pathogen interface: OMVs with long (smooth-type) lipopolysaccharide lipids retain their spherical shape when they interact with host cell membranes, whereasOMVs with shorter (rough-type) lipopolysaccharide lipids distort and spread over the host membrane surface. In addition, we show that OMVs preferentially coordinate domain-favoring ganglioside lipids within host membranes to enhance curvature and affect the local lipid composition. We predict that these differences in shape preservation affect OMV internalization on long timescales: spherical nanoparticles tend to be completely enveloped by host membranes, whereas low sphericity nanoparticles tend to remain on the surface of cells.

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Communication between the leaflets of asymmetric membranes revealed from coarse-grain molecular dynamics simulations

Cited by 27 publications

References 44 publications

Accurate In Silico Modeling of Asymmetric Bilayers Based on Biophysical Principles

Accurate In Silico Modeling of Asymmetric Bilayers Based on Biophysical Principles

BUMPy: A Model-Independent Tool for Constructing Lipid Bilayers of Varying Curvature and Composition

To infect or not to infect: molecular determinants of bacterial outer membrane vesicle internalization by host membranes

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