Biomedical Engineering Reference
In-Depth Information
FIGURE 2.3
Schematic of a membrane with a hydrophilic pore.
been able to show very similar structures to the pores described here. This
sounds promising in terms of confirming the theories regarding the creation of
pores and the mechanisms of electroporation in general, but some of the details
of the results of these simulations do not fully agree with the data recorded in
experiments. For instance, the fact that only relatively large transmembrane
voltages are able to simulate these pores raises concerns about the accuracy
of such simulations. A possible explanation to this specific problem may be
found in some impurities that usually exist in membranes but have not been
included in these simulations. Forces exerted on such impurities may enhance
the effect of water molecules that are being forced into the membrane due to
some nonuniformity in the electric field near the membrane-cytosol boundary.
Direct imaging of electroporation pores could possibly provide a convincing
proof to the theory of electroporation. Many attempts to do that have failed,
and in one case where the authors have claimed to have imaged pore using
freeze fracture electron microscopy techniques (Chang and Reese 1990) results
are inconclusive. The pores that are seen in this case may have been exper-
imental artifacts (Teissie et al. 2005). These images were not reproducible
under different circumstances and so the ultimate proof remains elusive.
The next stage is the stabilization. After the electric pulse has ended the
transmembrane potential decreases and the pores begin to reseal. This process
occurs very rapidly in the order of 1 msec or less. The permeability of the
membrane does not return to its original value. Although many of the pores
reseal with the removal of the external electric field, some of the larger pores
remain open for very long. This implies that, while most of the pores were
kept open because of the forces generated by the external electric field, some
of them took on a more stable configuration and they remain open and allow
general transport of molecules across the membrane.
The fourth stage of the process is resealing where the stable pores begin
to reseal and the membrane returns to a state very similar to its initial con-
figuration. This process may take several seconds and even minutes after the
termination of the pulse. Its duration is influenced by many factors such as
temperature, mechanical stress on the membrane, membrane composition,
and the chemical environment. For example, drugs that interfere with the
cytoskeleton of the cell, as well as other physical treatments that change its
organization, have a considerable effect on the resealing process. This may be
Search WWH ::
Custom Search