Evidence map›Paper›PMID 27551081›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Biophysical insight into mechanisms of sonoporation.

Brandon Helfield, Xucai Chen, Simon C Watkins, Flordeliza S Villanueva

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 1 pooled it
13.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

120 citing papers in PubMed, 1 synthesis or guideline pooled it, 284 citations in OpenAlex.

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60 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Brandon HelfieldCenter for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, PA 15213; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;
Xucai ChenCenter for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, PA 15213; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;
Simon C WatkinsCenter for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261.
Flordeliza S VillanuevaCenter for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, PA 15213; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213; villanuevafs@upmc.edu.
University of Pittsburgh · USUniversity of Pittsburgh Medical Center · US

Funding

Ultrasound-activated microbubbles for targeted siRNA delivery to tumorR01EB016516 · NIBIB · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VILLANUEVA, FLORDELIZA S · 2012 to 2015
$2.3M
Request for a Nikon A1 confocal microscopeS10OD019973 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATKINS, SIMON C · 2015 to 2015
$358k
NIBIB NIH HHS R01 EB016516NIH HHS S10 OD019973
6 · The paper itself

Abstract

This study presents a unique approach to understanding the biophysical mechanisms of ultrasound-triggered cell membrane disruption (i.e., sonoporation). We report direct correlations between ultrasound-stimulated encapsulated microbubble oscillation physics and the resulting cellular membrane permeability by simultaneous microscopy of these two processes over their intrinsic physical timescales (microseconds for microbubble dynamics and seconds to minutes for local macromolecule uptake and cell membrane reorganization). We show that there exists a microbubble oscillation-induced shear-stress threshold, on the order of kilopascals, beyond which endothelial cellular membrane permeability increases. The shear-stress threshold exhibits an inverse square-root relation to the number of oscillation cycles and an approximately linear dependence on ultrasound frequency from 0.5 to 2 MHz. Further, via real-time 3D confocal microscopy measurements, our data provide evidence that a sonoporation event directly results in the immediate generation of membrane pores through both apical and basal cell membrane layers that reseal along their lateral area (resealing time of ∼<2 min). Finally, we demonstrate the potential for sonoporation to indirectly initiate prolonged, intercellular gaps between adjacent, confluent cells (∼>30-60 min). This real-time microscopic approach has provided insight into both the physical, cavitation-based mechanisms of sonoporation and the biophysical, cell-membrane-based mechanisms by which microbubble acoustic behaviors cause acute and sustained enhancement of cellular and vascular permeability.

Indexed as

Biophysical PhenomenaUltrasonic WavesCell MembraneCell Membrane PermeabilityHumansMicrobubblesSonicationendothelial membranegene deliverymicrobubble contrast agentsonoporationultrasound therapy

Identifiers

PMID27551081
PMCPMC5018802
OpenAlexW2512809301

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.