Mechanism of pore formation in stearoyl-oleoyl-phosphatidylcholine membranes subjected to lateral tension

Akimov, Sergey A.; Aleksandrova, V. V.; Galimzyanov, Timur R.; Bashkirov, Pavel V.; Batishchev, Oleg V.

doi:10.1134/s1990747817030023

Cited by 3 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pore radius in these conditions is about 1 nm. This result is consistent with the previously obtained data on dependence of lipid pore energy on its radius [ 44 , 45 , 50 ]. According to these calculations, the energy of lipid pore has a minimum corresponding to the radius of ~1 nm; further increase of the radius results in abrupt increase of the deformation energy of the membrane.…”

Section: Discussionsupporting

confidence: 94%

“…We therefore contend that, in the π-shaped structure configuration, apposition of the membranes cannot end up in their fusion, and this trajectory of the process leads to a dead end state. As we demonstrated earlier, a hydrophilic pore in the membrane can be formed through an intermediate state of a hydrophobic defect [ 44 , 45 , 50 ]. In this state, lipid molecules shift radially in the plane of the membrane to form a water-filled cylinder piercing the entire membrane ( Figure 2 b).…”

Section: Resultsmentioning

confidence: 99%

“…The side surface of the cylinder is formed by the carbohydrate chains of lipid molecules. As the hydrophobic defect expands, polar headgroups of lipids “slip” into the lumen of the cylinder, ultimately forming a hydrophilic pore [ 44 , 45 , 50 ]. It takes crossing an energy barrier associated with the formation of a cylindrical hydrophobic defect, reorientation of the lipid molecules required to form the hydrophilic pore, and possibly a redistribution of the fusion peptides towards the pore edge.…”

Section: Resultsmentioning

confidence: 99%

“…In the case of stalk, the coordinate is the change of distance ∆ H between the fusion peptides and the transmembrane domains of the fusion proteins located in the target membrane and in the viral membrane, respectively ( Figure 2 a), while the radius of the hydrophobic patch ρ can vary freely. As we demonstrated earlier, the process of formation of a pore through the membrane is described by at least two coordinates [ 44 , 45 , 50 , 51 ]. In the case of the π-shaped structure, we selected the height of the hydrophobic part of the pore L , and the pore radius R p ( Figure 2 b) as the system coordinates.…”

Section: Resultsmentioning

confidence: 99%

“…The deformation energy of the membrane with a pore is calculated based on the elasticity theory approaches, similarly to calculations of the membrane deformation energy in the stalk configuration. More details about the formalism applied are available in [ 44 , 45 , 50 ].…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Molotkovsky

Galimzyanov

Jiménez-Munguía

et al. 2017

IJMS

View full text Add to dashboard Cite

Fusion of cellular membranes during normal biological processes, including proliferation, or synaptic transmission, is mediated and controlled by sophisticated protein machinery ensuring the preservation of the vital barrier function of the membrane throughout the process. Fusion of virus particles with host cell membranes is more sparingly arranged and often mediated by a single fusion protein, and the virus can afford to be less discriminative towards the possible different outcomes of fusion attempts. Formation of leaky intermediates was recently observed in some fusion processes, and an alternative trajectory of the process involving formation of π-shaped structures was suggested. In this study, we apply the methods of elasticity theory and Lagrangian formalism augmented by phenomenological and molecular geometry constraints and boundary conditions to investigate the traits of this trajectory and the drivers behind the choice of one of the possible scenarios depending on the properties of the system. The alternative pathway proved to be a dead end, and, depending on the parameters of the participating membranes and fusion proteins, the system can either reversibly enter the corresponding “leaky” configuration or be trapped in it. A parametric study in the biologically relevant range of variables emphasized the fusion protein properties crucial for the choice of the fusion scenario.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Molotkovsky

Galimzyanov

Jiménez-Munguía

et al. 2017

IJMS

View full text Add to dashboard Cite

show abstract

Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration

Haldar

Rice

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

To infect, enveloped viruses employ spike protein, spearheaded by its amphipathic fusion peptide (FP), that upon activation extends out beyond a forest of viral spikes to embed into the target cellular membrane. Here we report that isolated FP of influenza virus are membrane active by themselves generating pores in giant unilamellar vesicles and thus potentially explain both influenza virus' hemolytic activity and structure in cryo-electron tomography. Molecular dynamics simulations of asymmetric bilayers with different numbers of FP in one leaflet show substantial peptide clustering. At the center of this peptide condensate a profound change in the membrane structure results in thinning, higher water permeability, and curvature. In effect, a hybrid bilayer forms locally with one lipid monolayer and one peptide monolayer. Membrane elastic theory predicts that the energy landscape becomes favorable for spontaneous pore formation in this novel structure, consistent with the inhibition of pore formation by cholesterol observed experimentally.

show abstract

Continuum Models of Membrane Fusion: Evolution of the Theory

Akimov

Molotkovsky

Kuzmin

et al. 2020

IJMS

View full text Add to dashboard Cite

Starting from fertilization, through tissue growth, hormone secretion, synaptic transmission, and sometimes morbid events of carcinogenesis and viral infections, membrane fusion regulates the whole life of high organisms. Despite that, a lot of fusion processes still lack well-established models and even a list of main actors. A merger of membranes requires their topological rearrangements controlled by elastic properties of a lipid bilayer. That is why continuum models based on theories of membrane elasticity are actively applied for the construction of physical models of membrane fusion. Started from the view on the membrane as a structureless film with postulated geometry of fusion intermediates, they developed along with experimental and computational techniques to a powerful tool for prediction of the whole process with molecular accuracy. In the present review, focusing on fusion processes occurring in eukaryotic cells, we scrutinize the history of these models, their evolution and complication, as well as open questions and remaining theoretical problems. We show that modern approaches in this field allow continuum models of membrane fusion to stand shoulder to shoulder with molecular dynamics simulations, and provide the deepest understanding of this process in multiple biological systems.

show abstract

Mechanism of pore formation in stearoyl-oleoyl-phosphatidylcholine membranes subjected to lateral tension

Cited by 3 publications

References 32 publications

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration

Continuum Models of Membrane Fusion: Evolution of the Theory

Contact Info

Product

Resources

About