Cell responses without receptors and ligands, using nanosecond pulsed electric fields (nsPEFs)

Stephen J Beebe

Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk VA, USA

The plasma membrane is a lipid bilayer that surrounds and shelters the living structural and metabolic systems within cells. That membrane is replete with transmembrane proteins with and without ligand binding sites, oligosaccharides, and glycolipids on the cell exterior. Information transfer across this structure is closely controlled to maintain homeostasis and regulate cell responses to external stimuli. The plasma membrane is contiguous with the endoplasmic reticulum (ER) and nuclear membranes. A number of proteins form ER–mitochondria junctions, allowing interorganelle communications, especially for calcium transport. Transport mechanisms across these membranes include nongated channels or pores; single-gated channels for ion transport; carrier molecules for facilitated diffusion; and pumps for active transport of ions and macromolecules. During the activation of these transport systems, "pores" are formed through protein structures that transiently connect the intracellular and extracellular milieu. These pores are nanoscale structures with diameters of 0.2−4.0 nm. However, there can also be maligned movements of molecules across the plasma membranes. Staphylococcus aureus protein α-toxin and Streptococcus pyogenes protein streptolysin O both create pores that allow unsolicited molecular transfer across membranes that disrupts vital functions. Cytotoxic T-cells permeabilize the invading cell membranes with perforin, creating pores through which granzymes can induce apoptosis. These pores have a lumen of 5–30 nm with the majority at 13–20 nm.¹