Model of membrane fusion: Continuous transition to fusion pore with regard of hydrophobic and hydration interactions

Jiménez-Munguía

et al. 2017

IJMS

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.

Section: Resultsmentioning

confidence: 99%

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Molotkovsky

Jiménez-Munguía

et al. 2017

IJMS

“…Water density in the pore lumen is, in a sense, a parameter combining the radius and half-height of the hydrophobic belt. However, according to Marcelja approach, which we used for calculating the hydrophobic defect energy 28 , 29 , when the half-height of the hydrophobic belt is fixed, the order parameter of water, which is related to water density, monotonously changes with the belt radius. Thus, the radius and the half-height of the hydrophobic belt can be simultaneously changed in such a manner that the average water density in the pore lumen would remain constant, once again providing an example of two substantially different states of the system corresponding to the same value of the coordinate.…”

Section: Discussionmentioning

confidence: 99%

“…1B ). The energy of water-filled hydrophobic cylinder is calculated in the refs 13 , 28 based on Marcelja theory 29 . In our notation system the energy reads: where (4 πrL ) is the cylinder side surface area; σ h is macroscopic lateral tension at the surface separating lipid tails and water; ξ h ∼ 1 nm is characteristic length of hydrophobic interactions 30 ; I 0 , I 1 are Bessel functions of order zero and one, respectively.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pore formation in lipid membrane I: Continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore

Akimov

Volynsky

et al. 2017

Sci Rep

109

107

Lipid membranes serve as effective barriers allowing cells to maintain internal composition differing from that of extracellular medium. Membrane permeation, both natural and artificial, can take place via appearance of transversal pores. The rearrangements of lipids leading to pore formation in the intact membrane are not yet understood in details. We applied continuum elasticity theory to obtain continuous trajectory of pore formation and closure, and analyzed molecular dynamics trajectories of pre-formed pore reseal. We hypothesized that a transversal pore is preceded by a hydrophobic defect: intermediate structure spanning through the membrane, the side walls of which are partially aligned by lipid tails. This prediction was confirmed by our molecular dynamics simulations. Conversion of the hydrophobic defect into the hydrophilic pore required surmounting some energy barrier. A metastable state was found for the hydrophilic pore at the radius of a few nanometers. The dependence of the energy on radius was approximately quadratic for hydrophobic defect and small hydrophilic pore, while for large radii it depended on the radius linearly. The pore energy related to its perimeter, line tension, thus depends of the pore radius. Calculated values of the line tension for large pores were in quantitative agreement with available experimental data.

“…1B ). The energy of water-filled hydrophobic cylinder is calculated in the refs 14 , 18 based on Marcelja theory 19 as: where (4 πrL ) is the cylinder side surface area; σ h is macroscopic lateral tension at the surface separating lipid tails and water; ξ h ∼1 nm is characteristic length of hydrophobic interactions 20 ; I 0 , I 1 are Bessel functions of order zero and one, respectively.…”

Section: Continuum Theory Of Elasticitymentioning

confidence: 99%

Pore formation in lipid membrane II: Energy landscape under external stress

Akimov

Volynsky

et al. 2017

Sci Rep

Lipid membranes are extremely stable envelopes allowing cells to survive in various environments and to maintain desired internal composition. Membrane permeation through formation of transversal pores requires substantial external stress. Practically, pores are usually formed by application of lateral tension or transmembrane voltage. Using the same approach as was used for obtaining continuous trajectory of pore formation in the stress-less membrane in the previous article, we now consider the process of pore formation under the external stress. The waiting time to pore formation proved a non-monotonous function of the lateral tension, dropping from infinity at zero tension to a minimum at the tension of several millinewtons per meter. Transmembrane voltage, on the contrary, caused the waiting time to decrease monotonously. Analysis of pore formation trajectories for several lipid species with different spontaneous curvatures and elastic moduli under various external conditions provided instrumental insights into the mechanisms underlying some experimentally observed phenomena.