1 Department of Physics, Concordia University, Montreal, Quebec, Canada; Department of Biology, Concordia University, Montreal, Quebec, Canada.
2 Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
3 Department of Cell Biology, Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
4 Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Pittsburgh Heart and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address: villanuevafs@upmc.edu.

Transendothelial Perforations and the Sphere of Influence of Single-Site Sonoporation.

Ultrasound Med Biol. 2020 May 10;:

Authors: Helfield B, Chen X, Watkins SC, Villanueva FS

Abstract

Acoustically driven gas bubble cavitation locally concentrates energy and can result in physical phenomena including sonoluminescence and erosion. In biomedicine, ultrasound-driven microbubbles transiently increase plasma membrane permeability (sonoporation) to promote drug/gene delivery. Despite its potential, little is known about cellular response in the aftermath of sonoporation. In the work described here, using a live-cell approach, we assessed the real-time interplay between transendothelial perforations (~30-60 s) up to 650 µm2, calcium influx, breaching of the local cytoskeleton and sonoporation resealing upon F-actin recruitment to the perforation site (~5-10 min). Through biophysical modeling, we established the critical role of membrane line tension in perforation resealing velocity (10-30 nm/s). Membrane budding/shedding post-sonoporation was observed on complete perforation closure, yet successful pore repair does not mark the end of sonoporation: protracted cell mobility from 8 µs of ultrasound is observed up to 4 h post-treatment. Taken holistically, we established the biophysical context of endothelial sonoporation repair with application in drug/gene delivery.

PMID: 32402675 [PubMed - as supplied by publisher]