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.
Highlights
We focus on the parallel evolution of the theory of elasticity and models of the fusion processes in eukaryotic cells
The progress in the accumulation and systematization of experimental data on the fusion process and the development of theoretical approaches describing deformations of lipid membranes resulted in the development of fusion models that did not fit into that classical paradigm
Starting with the simplest theories that consider lipid monolayers as structureless surfaces characterized by bending stiffness only, fusion models became continuously more complicated as new data on the structure and physicochemical properties of membranes accumulated, the theory of elasticity of lipid bilayers improved, and a theoretical description of hydrophobic and hydration interactions was developed
Summary
To the best of our knowledge, the first work utilizing the generalized Helfrich model with an elastic energy functional written for separate membrane monolayers is devoted to a theoretical description of the membrane fusion process [48] This model ( referred to as the Kozlov-Markin model) assumes, for the first time, that the fusion of bilayer membranes occurs sequentially, monolayer by monolayer. Significant progress in the continuum theory was associated with the rapid parallel development of molecular dynamics methods, especially, the coarse-grained approximation [54,55,56] These methods allowed both visualizing intermediate structures of the fusion process and determining the elastic parameters of lipid membranes [54,55,56,57,58]. We focus on the parallel evolution of the theory of elasticity and models of the fusion processes in eukaryotic cells
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