Model of cell electrofusion. Membrane electroporation, pore coalescence and percolation.

نویسندگان

  • I P Sugar
  • W Förster
  • E Neumann
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Stochastic model for electric field-induced membrane pores. Electroporation.

Electric impulses (1-20 kV cm-1, 1-5 microseconds) cause transient structural changes in biological membranes and lipid bilayers, leading to apparently reversible pore formation ( electroporation ) with cross-membrane material flow and, if two membranes are in contact, to irreversible membrane fusion ( electrofusion ). The fundamental process operative in electroporation and electrofusion is tr...

متن کامل

The Influence of Vesicle Shape and Medium Conductivity on Possible Electrofusion under a Pulsed Electric Field

The effects of electric field on lipid membrane and cells have been extensively studied in the last decades. The phenomena of electroporation and electrofusion are of particular interest due to their wide use in cell biology and biotechnology. However, numerical studies on the electrofusion of cells (or vesicles) with different deformed shapes are still rare. Vesicle, being of cell size, can be...

متن کامل

Electroporation in Biological Cell and Tissue: An Overview

In this chapter, basics and mechanisms of electroporation are presented. Most important electric pulse parameters for electroporation efficiency for different applications that involve introduction of small molecules and macromolecules into the cell or cell membrane electrofusion are described. In all these applications, cell viability has to be preserved. However, in some biotechnological appl...

متن کامل

Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations.

Membrane electroporation is the method to directly transfer bioactive substances such as drugs and genes into living cells, as well as preceding electrofusion. Although much information on the microscopic mechanism has been obtained both from experiment and simulation, the existence and nature of possible intermediates is still unclear. To elucidate intermediates of electropore formation by dir...

متن کامل

Physical modelling of electroporation in close cell-to-cell proximity environments.

Many applications of electroporation, especially those utilizing electrofusion and in-vivo electroporation, involve cell environments that include close cell-to-cell proximity and a wide range of target cell size. It is important to understand how this kind of environment may alter optimum electroporation electrical parameters for any given application. A physical, electrically equivalent model...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Biophysical chemistry

دوره 26 2-3  شماره 

صفحات  -

تاریخ انتشار 1987