Molecular Dynamics Simulations of Curved Lipid Membranes

Larsen, Andreas Haahr

doi:10.3390/ijms23158098

Cited by 20 publications

(25 citation statements)

References 96 publications

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“…19,20 To resolve these issues, considerable effort has been put in the development of simulation setups that allow for the study of (preset) curved membranes. 21,22 Alternatively, bicelle systems were employed in the past to study the effect of peptides or proteins on the bicelle vesiculation rate as a measure for protein-induced membrane reshaping 20,23,24 or to quantify the protein-induced membrane curvature. 25 Spontaneous bicelle vesiculation was minimized or impeded by construction of rather small bicelles 25 or by minimizing the unfavorable edge tension by addition of shortchain lipids to the bicelle rim.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The study of spontaneous protein-induced membrane curvature is thereby impeded as well. A setup including membrane-shaping protein(s) in both ways with respect to the membrane normal may attenuate this periodicity-dependent stress. , To resolve these issues, considerable effort has been put in the development of simulation setups that allow for the study of (preset) curved membranes. , …”

Section: Introductionmentioning

confidence: 99%

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Lipid Bicelles in the Study of Biomembrane Characteristics

Pöhnl

Kluge²,

Böckmann

2023

J. Chem. Theory Comput.

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Simulations of lipid membranes typically make use of periodic boundary conditions to mimic macroscopically sized membranes and allow for comparison to experiments performed e.g. on planar lipid membranes or on unilamellar lipid vesicles. However, the lateral periodicity partly suppresses membrane fluctuations or membrane remodeling, processes that are of particular importance in the study of asymmetric membranes–i.e. membranes with integral or associated proteins and/or asymmetric lipid compositions. Here, we devised a simple albeit powerful lipid bicelle model system that (i) displays similar structural, dynamical, and mechanical properties compared to infinite periodic lipid membrane systems and allows (ii) for the study of asymmetric lipid bilayer systems and (iii) the unperturbed formation of local spontaneous curvature induced by lipids or proteins in molecular dynamics simulations. In addition, the system is characterized by largely unbiased thermal fluctuations as opposed to standard bilayer systems. Application of the bicelle system for an asymmetric lipid composition resembling the plasma membrane reveals that the cholesterol density for a tension-free plasma membrane with a vanishing spontaneous curvature is larger by 28% within the extracellular leaflet compared to the cytosolic leaflet.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipid Bicelles in the Study of Biomembrane Characteristics

Pöhnl

Kluge²,

Böckmann

2023

J. Chem. Theory Comput.

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“…Nonetheless, this protein motion is not strong enough to cause changes in the membrane curvature or other membrane damage. We expect that membrane-bound mGBP2 multimers are needed to cause membrane damage 57,58 , which will be addressed in our future work.…”

Section: Discussionmentioning

confidence: 99%

Domain motions, dimerization, and membrane interactions of the murine guanylate binding protein 2

Loschwitz

Steffens

Wang

et al. 2023

Sci Rep

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Guanylate-binding proteins (GBPs) are a group of GTPases that are induced by interferon-$$\gamma$$ γ and are crucial components of cell-autonomous immunity against intracellular pathogens. Here, we examine murine GBP2 (mGBP2), which we have previously shown to be an essential effector protein for the control of Toxoplasma gondii replication, with its recruitment through the membrane of the parasitophorous vacuole and its involvement in the destruction of this membrane likely playing a role. The overall aim of our work is to provide a molecular-level understanding of the mutual influences of mGBP2 and the parasitophorous vacuole membrane. To this end, we performed lipid-binding assays which revealed that mGBP2 has a particular affinity for cardiolipin. This observation was confirmed by fluorescence microscopy using giant unilamellar vesicles of different lipid compositions. To obtain an understanding of the protein dynamics and how this is affected by GTP binding, mGBP2 dimerization, and membrane binding, assuming that each of these steps are relevant for the function of the protein, we carried out standard as well as replica exchange molecular dynamics simulations with an accumulated simulation time of more than 30 μs. The main findings from these simulations are that mGBP2 features a large-scale hinge motion in its M/E domain, which is present in each of the studied protein states. When bound to a cardiolipin-containing membrane, this hinge motion is particularly pronounced, leading to an up and down motion of the M/E domain on the membrane, which did not occur on a membrane without cardiolipin. Our prognosis is that this up and down motion has the potential to destroy the membrane following the formation of supramolecular mGBP2 complexes on the membrane surface.

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“…Analysis by all‐atom MD remains not easy even using current state‐of‐art computation systems. Models may be presented by coarse‐grained simulations, [16e,f] however, questions remain about the relevance to real molecules [7b,17] . Therefore, a better knowledge of the curvature‐inducing mechanism by EpN18 using systematically designed analogs will impact our understanding of membrane structure regulation mechanisms utilized by these proteins and peptides in general.…”

Section: Introductionmentioning

confidence: 99%

Structural Dissection of Epsin‐1 N‐Terminal Helical Peptide: The Role of Hydrophobic Residues in Modulating Membrane Curvature

Nishimura

Kawaguchi

Kuroki

et al. 2023

Chemistry A European J

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Spatiotemporal structural alterations in cellular membranes are the hallmark of many vital processes. In these cellular events, the induction of local changes in membrane curvature often plays a pivotal role. Many amphiphilic peptides are able to modulate membrane curvature, but there is little information on specific structural factors that direct the curvature change. Epsin‐1 is a representative protein thought to initiate invagination of the plasma membrane upon clathrin‐coated vesicles formation. Its N‐terminal helical segment (EpN18) plays a key role in inducing positive membrane curvature. This study aimed to elucidate the essential structural features of EpN18 in order to better understand general curvature‐inducing mechanisms, and to design effective tools for rationally controlling membrane curvature. Structural dissection of peptides derived from EpN18 revealed the decisive contribution of hydrophobic residues to (i) enhancing membrane interactions, (ii) helix structuring, (iii) inducing positive membrane curvature, and (iv) loosening lipid packing. The strongest effect was obtained by substitution with leucine residues, as this EpN18 analog showed a marked ability to promote the influx of octa‐arginine cell‐penetrating peptides into living cells.

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Molecular Dynamics Simulations of Curved Lipid Membranes

Cited by 20 publications

References 96 publications

Lipid Bicelles in the Study of Biomembrane Characteristics

Lipid Bicelles in the Study of Biomembrane Characteristics

Domain motions, dimerization, and membrane interactions of the murine guanylate binding protein 2

Structural Dissection of Epsin‐1 N‐Terminal Helical Peptide: The Role of Hydrophobic Residues in Modulating Membrane Curvature

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