Dynamics of fusion pores connecting membranes of different tensions

The energetics underlying the expansion of fusion pores connecting biologic al or lipid bilayer membranes is elucidated. The energetics necessary to de form membranes as the pore enlarges, in some combination with the action of the fusion proteins, must determine pore growth. The dynamics of pore grow th is considered for the case of two homogeneous fusing membranes under dif ferent tensions. It is rigorously shown that pore growth can be quantitativ ely described by treating the pore as a quasiparticle that moves in a mediu m with a viscosity determined by that of the membranes. Motion is subject t o tension, bending, and viscous forces. Pore dynamics and lipid flow throug h the pore were calculated using Lagrange's equations, with dissipation cau sed by intra- and intermonolayer friction. These calculations show that the energy barrier that restrains pore enlargement depends only on the sum of the tensions; a difference in tension between the fusing membranes is irrel evant. in contrast, lipid flux through the fusion pore depends on the tensi on difference but is independent of the sum. Thus pore growth is not affect ed by tension-driven lipid flux from one membrane to the other. The calcula tions of the present study explain how increases in tension through osmotic swelling of vesicles cause enlargement of pores between the vesicles and p lanar bilayer membranes. In a similar fashion, swelling of secretory granul es after fusion in biological systems could promote pore enlargement during exocytosis. The calculations also show that pore expansion can be caused b y pore lengthening; lengthening may be facilitated by fusion proteins.