title: Microbubble-Assisted Ultrasound-Induced Transient Phosphatidylserine Translocation.
abstract: Microbubble-assisted ultrasound (sonopermeabilization) results in reversible permeabilization of the plasma membrane of cells. This method is increasingly used in vivo because of its potential to deliver therapeutic molecules with limited cell damage. Nevertheless, the effects of sonopermeabilization on the plasma membrane remain not fully understood. We investigated the influence of sonopermeabilization on the transverse mobility of phospholipids, especially on phosphatidylserine (PS) externalization. We performed studies using optical imaging with Annexin V and FM1-43 probes to monitor PS externalization of rat glioma C6 cells. Sonopermeabilization induced transient membrane permeabilization, which is positively correlated with reversible PS externalization. This membrane disorganization was temporary and not associated with loss of cell viability. Sonopermeabilization did not induce PS externalization via activation of the scramblase. We hypothesize that acoustically induced membrane pores may provide a new pathway for PS migration between both membrane leaflets. During the membrane-resealing phase, PS asymmetry may be re-established by amino-phospholipid flippase activity and/or endocytosis, along with exocytosis processes.
authors.affiliation: Imaging Division, UMC Utrecht, Utrecht, The Netherlands. Electronic address: jean-michel.escoffre@univ-tours.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Escoffre
authors.affiliation: Imaging Division, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Derieppe
authors.affiliation: Imaging Division, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Lammertink
authors.affiliation: Imaging Division, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: Bos
authors.affiliation: Imaging Division, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Chrit
authors.initials: C
authors.lastname: Moonen
mesh_terms: D000818:Animals; D002470:Cell Survival; D003287:Contrast Media / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D045423:Microbubbles; D010539:Permeability; D010718:Phosphatidylserines / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D013459:Sulfur Hexafluoride / Q000378:metabolism*; D000069453:Ultrasonic Waves
chemical_list: D003287:Contrast Media; D010718:Phosphatidylserines; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride
keywords: Membrane permeabilization; Microbubble; Phosphatidylserine externalization; Ultrasound