title: Reparable Cell Sonoporation in Suspension: Theranostic Potential of Microbubble.
abstract: The conjunction of low intensity ultrasound and encapsulated microbubbles can alter the permeability of cell membrane, offering a promising theranostic technique for non-invasive gene/drug delivery. Despite its great potential, the biophysical mechanisms of the delivery at the cellular level remains poorly understood. Here, the first direct high-speed micro-photographic images of human lymphoma cell and microbubble interaction dynamics are provided in a completely free suspension environment without any boundary parameter defect. Our real-time images and theoretical analyses prove that the negative divergence side of the microbubble's dipole microstreaming locally pulls the cell membrane, causing transient local protrusion of 2.5 µm in the cell membrane. The linear oscillation of microbubble caused microstreaming well below the inertial cavitation threshold, and imposed 35.3 Pa shear stress on the membrane, promoting an area strain of 0.12%, less than the membrane critical areal strain to cause cell rupture. Positive transfected cells with pEGFP-N1 confirm that the interaction causes membrane poration without cell disruption. The results show that the overstretched cell membrane causes reparable submicron pore formation, providing primary evidence of low amplitude (0.12 MPa at 0.834 MHz) ultrasound sonoporation mechanism.
authors.affiliation: 1. Department of Anatomy, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan;; 2. Bioelectrics Department, Institute of Pulsed Power Science, Kumamoto University, Kumamoto 860-8555, Japan.
authors.forename: S Moosavi
authors.initials: SM
authors.lastname: Nejad
authors.affiliation: 2. Bioelectrics Department, Institute of Pulsed Power Science, Kumamoto University, Kumamoto 860-8555, Japan.
authors.forename: Hamid
authors.initials: H
authors.lastname: Hosseini
authors.affiliation: 2. Bioelectrics Department, Institute of Pulsed Power Science, Kumamoto University, Kumamoto 860-8555, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: 1. Department of Anatomy, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan;
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tachibana
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology* / Q000528:radiation effects*; D017930:Genes, Reporter; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D045423:Microbubbles; D018715:Microscopy, Video; D010539:Permeability / Q000528:radiation effects*; D010957:Plasmids; D013010:Sonication / Q000379:methods*; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014162:Transfection
keywords: Cell suspension.; Dipole microstreaming; Low amplitude ultrasound; Reparable sonoporation