The article discusses the mechanics of membrane fusion, focusing on the fusion-through-hemifusion pathway. It reviews the structures and energies of fusion intermediates in protein-free lipid bilayers, highlighting the role of membrane stresses in controlling the fusion process. The study identifies hemifusion structures and fusion pores as key intermediates, with hemifusion involving connections between outer leaflets of apposed membranes and fusion pores connecting both outer and inner leaflets. The formation of fusion pores is influenced by lipid composition, with lipids like lysophosphatidylcholine (LPC) and phosphatidylethanolamine affecting the curvature of lipid monolayers. The article also explores the conditions under which lipid bilayers fuse, including the importance of close inter-bilayer contact and membrane tension. Physical modeling of membrane fusion is discussed, with two main approaches: the continuum approach, which models membranes as continuous films, and the simulation approach, which uses computational methods to study fusion processes. The study highlights the differences between these approaches, noting that the continuum approach assumes axially symmetric shapes for fusion intermediates, while simulations are less constrained. The article also discusses the role of protein fusion machinery in membrane fusion, emphasizing the importance of membrane stresses and the involvement of fusion peptides and transmembrane domains. The study concludes that the fusion-through-hemifusion pathway is a conserved mechanism in biological membrane fusion, driven by membrane stresses and involving the formation of hemifusion structures and fusion pores. The article also discusses the mechanisms by which proteins promote fusion, including the generation of membrane curvature and the role of fusion peptides in facilitating membrane deformation. Overall, the study provides a comprehensive overview of the mechanics of membrane fusion, highlighting the importance of lipid composition, membrane stresses, and protein interactions in the process.The article discusses the mechanics of membrane fusion, focusing on the fusion-through-hemifusion pathway. It reviews the structures and energies of fusion intermediates in protein-free lipid bilayers, highlighting the role of membrane stresses in controlling the fusion process. The study identifies hemifusion structures and fusion pores as key intermediates, with hemifusion involving connections between outer leaflets of apposed membranes and fusion pores connecting both outer and inner leaflets. The formation of fusion pores is influenced by lipid composition, with lipids like lysophosphatidylcholine (LPC) and phosphatidylethanolamine affecting the curvature of lipid monolayers. The article also explores the conditions under which lipid bilayers fuse, including the importance of close inter-bilayer contact and membrane tension. Physical modeling of membrane fusion is discussed, with two main approaches: the continuum approach, which models membranes as continuous films, and the simulation approach, which uses computational methods to study fusion processes. The study highlights the differences between these approaches, noting that the continuum approach assumes axially symmetric shapes for fusion intermediates, while simulations are less constrained. The article also discusses the role of protein fusion machinery in membrane fusion, emphasizing the importance of membrane stresses and the involvement of fusion peptides and transmembrane domains. The study concludes that the fusion-through-hemifusion pathway is a conserved mechanism in biological membrane fusion, driven by membrane stresses and involving the formation of hemifusion structures and fusion pores. The article also discusses the mechanisms by which proteins promote fusion, including the generation of membrane curvature and the role of fusion peptides in facilitating membrane deformation. Overall, the study provides a comprehensive overview of the mechanics of membrane fusion, highlighting the importance of lipid composition, membrane stresses, and protein interactions in the process.