Broad pore lifetime distributions: A fundamental concept for cell electroporation

Abstract

We describe a concept that has the potential to change how we think about the underlying mechanisms of cell membrane electroporation (EP). Prior experimental, theoretical and modeling have emphasized a single pore lifetime as adequate for particular conditions. Here we introduce a much more complex response: The rapid creation of many types of pore structures, of which some are traditional transient lipidic pores (TPs), but the great majority are complex pores (CPs) based on both lipids and other molecules or molecular segments. At the inner leaflet of the cell plasma membrane (PM) non-lipidic molecules come from the over-crowded cytoplasm. At the outer leaflet they originate from the extracellular medium and extracellular matrix. Some partially or fully insert into TPs during or shortly after TP formation, or bind to the membrane nearby. This process is complex, leading to mostly short-lived structures, with relatively few lasting for long times. We speculate that the characteristic pore lifetimes range from $\sim$100 ns to 1,000 s, based on implications from experiments. The frequency-of-occurrence probably falls off extremely rapidly with increasing lifetime, $\tau_{CP}$, which implies that most are inaccessible to traditional experimental methods. It also suggests that unexpected behavior can occur early in pulsing, vanishing before post-pulse observations begin.