Model of cell electrofusion. Membrane electroporation, pore coalescence and percolation.
High electric field impulses (1-20 kV/cm, 1-20 microseconds) may trigger fusion between adhering cells or lipid vesicles (electrofusion). In this paper a qualitative model of electrofusion is proposed consistent with both electron and light microscopic data. Electrofusion is considered as a multistep process comprising tight membrane-contact formation, membrane electroporation as well as an alternating series of subsequent fast collective and slow diffusive fusion stages. The following sequence of steps is suggested: The electric field pulse enforces (via polarization) a tight contact between the membranes of the cells or vesicles to be fused. During tight-contact formation between the opposing membrane surfaces the membrane-adherent water layers are partially squeezed out from the intermembraneous space. Pores are formed in the double membrane contact area (electroporation) involving lateral diffusion and rotation of the lipid molecules in both adhering membrane parts. With increasing pore density, pore-pore interactions lead to short-range coalescence of double membrane pores resulting in ramified cracks; especially small tongues and loops are formed. At supercritical pore density long-range coalescence of the pores occurs (percolation) producing one large double membrane loop (or tongue) and subsequently one large hole in the contact area. After switching off the electric field, the smaller pores, tongues and loops reseal and water flows back into the intermembraneous space of the double membrane in the contact area. As a consequence of the increasing membrane-membrane separation due to water backflow, cooperative rounding of the edges of remaining larger tongues and holes occurs. This results in the formation of an intercellular cytoplasm bridge (channel) concomitant with the disappearance of the contact line between the fusing cells. The membrane parts surrounded by continuous loop-like cracks may separate from the system and may finally form vesicles. Our electrofusion model comprises a strong linkage between the membrane pore formation by high electric fields (electroporation) and the process of electrofusion. Additionally, both pore-pore interactions as well as protein-protein interactions in the contact area of the fusing cells are explicitly introduced. The model provides a qualitative molecular description of basic experimental observations such as the production of membrane fragments, of smaller inside-out vesicles and the formation of larger intercellular cytoplasm bridges.
D002463:Cell Membrane Permeability; D004553:Electric Conductivity; D004563:Electrochemistry; D008081:Liposomes; D008954:Models, Biological; D008968:Molecular Conformation; D013499:Surface Properties
D008081:Liposomes