Publication
Title
Targeted perturbation of nuclear envelope integrity with vapor nanobubble-mediated photoporation
Author
Abstract
The nuclear envelope (NE) has long been considered to dismantle only during mitosis. However, recent observations in cancer cells and laminopathy patient cells have revealed that the NE can also transiently rupture during interphase, thereby perturbing cellular homeostasis. Although NE ruptures are promoted by mechanical force and the loss of lamins, their stochastic nature and variable frequency preclude the study of their direct downstream consequences. We have developed a method based on vapor nanobubble-mediated photoporation that allows for deliberately inducing NE ruptures in a spatiotemporally controlled manner. Our method relies on wide-field laser illumination of perinuclear gold nanoparticles, resulting in the formation of short-lived vapor nanobubbles that inflict minute mechanical damage to the NE, thus creating small pores. We demonstrate that perinuclear localization of gold nanoparticles can be achieved after endocytic uptake or electroporation-facilitated delivery and that both strategies result in NE rupture upon laser irradiation. Furthermore, we prove that photoporation-induced nuclear ruptures are transient and recapitulate hallmarks of spontaneous NE ruptures that occur in A-type lamin-depleted cells. Finally, we show that the same approach can be used to promote influx of macromolecules that are too large to passively migrate through the NE. Thus, by providing unprecedented control over nuclear compartmentalization, nuclear photoporation offers a powerful tool for both fundamental cell biology research and drug delivery applications.
Language
English
Source (journal)
ACS nano. - -
Publication
2018
ISSN
1936-0851
DOI
10.1021/ACSNANO.8B01860
Volume/pages
12 :8 (2018) , p. 7791-7802
ISI
000443525600032
Pubmed ID
30001106
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Research in the field of the advanced biomedical microscopic imaging: "Towards medical cytomics. Paving the way with nextgeneration microscopy".
Unveiling the role of nuclear compartmentalisation in laminopathies with intelligent high content imaging and spatial proteomics.
Border control: getting a grip on nuclear envelope rupture and repair.
NANOBUBBLE: Laser-induced vapour nanobubbles for intracellular delivery of nanomaterials and treatment of biofilm infections
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 24.07.2018
Last edited 02.10.2024
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