Continuum Models of Membrane Fusion: Evolution of the Theory

Abstract

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.

Interaction of Peptides Containing CRAC Motifs with Lipids in Membranes of Various Composition

“…Clustering of various proteins and lipids in a limited area of the plasma membrane is necessary for the normal course of vital cellular processes, in particular, membrane fusion and fission [15,16], the transmission of cellular signals [17,18], etc. In addition to normal physiological processes, such an organization of lipid-protein platforms is a key stage in pathological processes: the assembly of new viral particles on the membranes of a cell infected with enveloped viruses.…”

Ectodomain Pulling Combines with Fusion Peptide Inserting to Provide Cooperative Fusion for Influenza Virus and HIV

“…The elastic energy of such protrusions is of the order of 10 k B T [ 33 , 47 ], meaning that the system of even small synthetic peptides is able to develop such mechanical efforts in the course of membrane fusion. The main role of fusogens is to bring merging membranes into close local contact to allow overcoming the hydration repulsion barrier of two lipid bilayers [ 23 ]. The characteristic energy of this process is mainly determined by the physicochemical properties of lipid membranes (e.g., polarity, elastic moduli), and thus, it may be expected that the functional mechanisms of most fusogens in various systems should be rather similar; the differences might be dictated by the very specific requirements of fusion parameters in particular system (e.g., the rate or efficiency of fusion).…”

“…The fusion of biological membranes requires the close contact of two lipid bilayers to overcome the hydration repulsion between them, which is minimized by decreasing their area of contact at a fusion site. Further remodeling is accompanied with strong deformations of the lipid matrix [ 9 , 23 ]. Thus, membrane merger is an energetically expensive process, prohibiting spontaneous fusion.…”

“…Basing on these data, in numerous works, it is proposed that the role of fusion proteins is merely to bring the membranes into close contact, while the rate of the rest of the fusion process is mainly determined by the energy of elastic deformations of fusing lipid bilayers [ 20 ]. Multiple theoretical models are devoted to estimation of the elastic energy of intermediate states of the fusion process [ 20 , 21 , 22 , 23 ]. It is shown that the main energy barrier of hemifusion strongly depends on the distance between two fusing membranes: the larger the distance, the higher the barrier [ 20 , 21 ].…”

Biomimetic Curvature and Tension-Driven Membrane Fusion Induced by Silica Nanoparticles

“…In membrane fusion events, lipid packing defects are considered as an initial step required for two adjacent membranes to fuse. 30,37,38 Since previous studies on NP-membrane interactions have shown that SiO2 NPs produce perturbations in lipid packing and membrane fluidity, 31,33,39 we used Laurdan spectral imaging to quantify changes in lipid packing and membrane hydration of DOPC GUVs labelled with 0.5 mol% Laurdan after incubation with 25 µg/ml SiO2 NPs.…”