Optimization of hydrophobic nanoparticles to better target lipid rafts with molecular dynamics simulations

Nanoscale ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 4101-4109 ◽  
Author(s):  
Xiaoqian Lin ◽  
Xubo Lin ◽  
Ning Gu
Keyword(s):  
Molecular Dynamics ◽  
Plasma Membrane ◽  
Molecular Dynamics Simulations ◽  
Lipid Rafts ◽  
Membrane Domains ◽  
Dynamics Simulations

Due to different interactions between lipids and proteins, a plasma membrane can segregate into different membrane domains.

Surface Ligand Rigidity Modulates Lipid Raft Affinity of Ultra-small Hydrophobic Nanoparticles: Insights from Molecular Dynamics Simulations

Nanoscale ◽  
2021 ◽  
Author(s):  
Xiaoqian Lin ◽  
Xubo Lin
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
The Other ◽  
Membrane Domains ◽  
Surface Ligand ◽  
Proper Functions ◽  
Dynamics Simulations ◽  
Small Hydrophobic

Differential preferences between lipids and proteins drive the formation of dynamical nanoscale membrane domains (lipid rafts), which play key roles in proper functions of the cell. On the other hand,...

scholarly journals Differences and commonalities in plasma membrane recruitment of the two morphogenetically distinct retroviruses HIV-1 and MMTV

2020 ◽  
Vol 295 (26) ◽  
pp. 8819-8833 ◽  
Author(s):  
Petra Junková ◽  
Roman Pleskot ◽  
Jan Prchal ◽  
Jakub Sýs ◽  
Tomáš Ruml
Keyword(s):  
Molecular Dynamics ◽  
Plasma Membrane ◽  
Molecular Dynamics Simulations ◽  
Hydrophobic Interactions ◽  
Membrane Binding ◽  
Membrane Topology ◽  
Membrane Targeting ◽  
Surface Mapping ◽  
Dynamics Simulations ◽  
Hiv 1

Retroviral Gag polyproteins are targeted to the inner leaflet of the plasma membrane through their N-terminal matrix (MA) domain. Because retroviruses of different morphogenetic types assemble their immature particles in distinct regions of the host cell, the mechanism of MA-mediated plasma membrane targeting differs among distinct retroviral morphogenetic types. Here, we focused on possible mechanistic differences of the MA-mediated plasma membrane targeting of the B-type mouse mammary tumor virus (MMTV) and C-type HIV-1, which assemble in the cytoplasm and at the plasma membrane, respectively. Molecular dynamics simulations, together with surface mapping, indicated that, similarly to HIV-1, MMTV uses a myristic switch to anchor the MA to the membrane and electrostatically interacts with phosphatidylinositol 4,5-bisphosphate to stabilize MA orientation. We observed that the affinity of MMTV MA to the membrane is lower than that of HIV-1 MA, possibly related to their different topologies and the number of basic residues in the highly basic MA region. The latter probably reflects the requirement of C-type retroviruses for tighter membrane binding, essential for assembly, unlike for D/B-type retroviruses, which assemble in the cytoplasm. A comparison of the membrane topology of the HIV-1 MA, using the surface-mapping method and molecular dynamics simulations, revealed that the residues at the HIV-1 MA C terminus help stabilize protein–protein interactions within the HIV-1 MA lattice at the plasma membrane. In summary, HIV-1 and MMTV share common features such as membrane binding of the MA via hydrophobic interactions and exhibit several differences, including lower membrane affinity of MMTV MA.

scholarly journals Assessing the extent of the structural and dynamic modulation of membrane lipids due to pore forming toxins: insights from molecular dynamics simulations

Soft Matter ◽  
2020 ◽  
Vol 16 (20) ◽  
pp. 4840-4857 ◽  
Author(s):  
Vadhana Varadarajan ◽  
Rajat Desikan ◽  
K. G. Ayappa
Keyword(s):  
Molecular Dynamics ◽  
Plasma Membrane ◽  
Molecular Dynamics Simulations ◽  
Bacterial Infections ◽  
Membrane Lipids ◽  
Dynamic Modulation ◽  
Structure And Dynamics ◽  
Transmembrane Pores ◽  
Dynamics Simulations

Pore forming toxins released during bacterial infections form transmembrane pores disrupting the structure and dynamics of lipids in the plasma membrane.

scholarly journals Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine

2019 ◽  
Author(s):  
Semen Yesylevskyy ◽  
Timothée Rivel ◽  
Christophe Ramseyer
Keyword(s):  
Molecular Dynamics ◽  
Plasma Membrane ◽  
Molecular Dynamics Simulations ◽  
Membrane Curvature ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Membrane Bending ◽  
Dynamics Simulations

ABSTRACTIn this work the permeability of a model asymmetric plasma membrane, for ions, water and the anti-cancer drugs cisplatin and gemcitabine is studied by means of all-atom molecular dynamics simulations. It is shown that permeability of the membranes increases from one to three orders of magnitude upon membrane bending depending on the compound and the sign of curvature. Our results show that the membrane curvature is an important factor which should be considered during evaluation of drug translocation.TOC GRAPHICS

scholarly journals Identification of electroporation sites in the complex lipid organization of the plasma membrane

2021 ◽  
Author(s):  
Lea Rems ◽  
Xinru Tang ◽  
Fangwei Zhao ◽  
Sergio Perez-Conesa ◽  
Ilaria Testa ◽  
...  
Keyword(s):  
Machine Learning ◽  
Molecular Dynamics ◽  
Plasma Membrane ◽  
Survival Analysis ◽  
Electric Field ◽  
Molecular Dynamics Simulations ◽  
Coarse Grained ◽  
Machine Learning Methods ◽  
Lipid Organization ◽  
Dynamics Simulations

The plasma membrane of a biological cell is a complex assembly of lipids and membrane proteins, which tightly regulate transmembrane transport. When a cell is exposed to a strong electric field, the membrane integrity becomes transiently disrupted by formation of transmembrane pores. This phenomenon, termed electroporation, is already utilized in many rapidly developing applications in medicine including gene therapy, cancer treatment, and treatment of cardiac arrythmias. However, the molecular mechanisms of electroporation are not yet sufficiently well understood; in particular, it is unclear where exactly pores form in the complex organization of the plasma membrane. In this study we combine coarse-grained molecular dynamics simulations, machine learning methods, and Bayesian survival analysis to identify how formation of pores depends on the local lipid organization. We show that pores do not form homogeneously across the membrane, but colocalize with domains that have specific features, the most important being high density of polyunsaturated lipids. We further show that knowing the lipid organization is sufficient to reliably predict poration sites with machine learning. However, by analysing poration kinetics with Bayesian survival analysis we then show that poration does not depend solely on local lipid arrangement, but also on membrane mechanical properties and the polarity of the electric field. Finally, we discuss how the combination of atomistic and coarse-grained molecular dynamics simulations, machine learning methods, and Bayesian survival analysis can guide the design of future experiments and help us to develop an accurate description of plasma membrane electroporation on the whole-cell level. Achieving this will allow us to shift the optimization of electroporation applications from blind trial-and-error approaches to mechanistic-driven design.

scholarly journals Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Semen Yesylevskyy ◽  
Timothée Rivel ◽  
Christophe Ramseyer
Keyword(s):  
Molecular Dynamics ◽  
Plasma Membrane ◽  
Molecular Dynamics Simulations ◽  
Membrane Curvature ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Membrane Bending ◽  
Dynamics Simulations ◽  
Curved Membrane ◽  
First Time

AbstractIn this work the permeability of a model asymmetric plasma membrane, for ions, water and the anti-cancer drugs cisplatin and gemcitabine is studied by means of all-atom molecular dynamics simulations. It is shown for the first time that permeability of the highly curved membrane increases from one to three orders of magnitude upon membrane bending depending on the compound and the sign of curvature. Our results suggest that the membrane curvature could be an important factor of drug translocation through the membrane.

scholarly journals Correction: Optimization of hydrophobic nanoparticles to better target lipid rafts with molecular dynamics simulations

Nanoscale ◽  
2020 ◽  
Vol 12 (30) ◽  
pp. 16389-16389
Author(s):  
Xiaoqian Lin ◽  
Xubo Lin ◽  
Ning Gu
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Rafts ◽  
Dynamics Simulations

Correction for ‘Optimization of hydrophobic nanoparticles to better target lipid rafts with molecular dynamics simulations’ by Xiaoqian Lin et al., Nanoscale, 2020, 12, 4101–4109, DOI: 10.1039/C9NR09226A.

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