title: Ultrastructural modifications of cell membranes induced by "electroporation" on melanoma xenografts.
abstract: Electroporation (EP) has been widely employed in the past years as a safe and effective technique to drive drugs and DNA plasmids into target cells both for experimental and therapeutic purposes. Despite the large bulk of literature on this topic, often describing successful outcomes, there is a lack of knowledge about the intimate mechanism(s) controlling this phenomenon. In this paper, we describe a number of ultrastructural alterations in the cellular membranes following the exposure of orthotopic melanomas and red blood cells to trains of biphasic pulses. Specifically, melanoma xenografts grown in nude mice were subject to trains of eight biphasic pulses using an electric field of 1250 or 2450 V/cm, excised after 5 min and processed for electron microscopy. The freeze-fracturing analysis of both cell types evidenced defects in the dynamic assembly of lipids and proteins, which generate "areas with rough structure" and intensive clustering of intramembrane proteins. Such modifications could be the hallmarks of lipid and protein alterations, of protein cohesion reduction, and of changes in lipid orientation inside cell membranes, as postulated in several mathematical models applied to electroporation, and warrant further investigations.
authors.affiliation: SAFU Department, Regina Elena Cancer Institute, Rome, Italy. info@enricospugnini.net
authors.forename: Enrico P
authors.initials: EP
authors.lastname: Spugnini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Arancia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Porrello
authors.forename: Marisa
authors.initials: M
authors.lastname: Colone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Formisano
authors.forename: Annarita
authors.initials: A
authors.lastname: Stringaro
authors.forename: Gennaro
authors.initials: G
authors.lastname: Citro
authors.forename: Agnese
authors.initials: A
authors.lastname: Molinari
mesh_terms: D000818:Animals; D002415:Cats; D002462:Cell Membrane; D018274:Electroporation / Q000295:instrumentation / Q000379:methods*; D004912:Erythrocytes / Q000648:ultrastructure*; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured