Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

Geiger, R C; Taylor, W; Glucksberg, M R; Dean, D A

doi:10.1038/sj.gt.3302693

Cited by 64Cellular Mechanics and InteractionsRNA Interference and Gene DeliveryVirus-based gene therapy research

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

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Geiger, R C, Taylor, W, Glucksberg, M R, Dean, D A·2006·Gene Therapy

DOI 10.1038/sj.gt.3302693PMC PMC4150916

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Abstract

Cyclic stretch is known to alter a number of cellular and subcellular processes, including those involved in nonviral gene delivery. We have previously shown that moderate equibiaxial cyclic stretch (10% change in basement membrane area, 0.5 Hz, 50% duty cycle) of human pulmonary A549 cells enhances gene transfer and expression of reporter plasmid DNA in vitro, and that this phenomena may be due to alterations in cytoplasmic trafficking. Although the path by which plasmid DNA travels through the cytoplasm toward the nucleus is not well understood, the cytoskeleton and the constituents of the cytoplasm are known to significantly hinder macromolecular diffusion. Using biochemical techniques and immunofluorescence microscopy, we show that both the microfilament and microtubule networks are significantly reorganized by equibiaxial cyclic stretch. Prevention of this reorganization through the use of cytoskeletal stabilizing compounds mitigates the stretch-induced increase in gene expression, however, depolymerization in the absence of stretch is not sufficient to increase gene expression. These results suggest that cytoskeletal reorganization plays an important role in stretch-induced gene transfer and expression.

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Disruption or reorganization of actin cytoskeleton, or depletion of keratin and vimentin, significantly increases diffusion of gene payloads.
“Disruption or reorganization of the actin cytoskeleton, or depletion of keratin and vimentin in cells, significantly increases the diffusion of gene payloads [190–192].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [192]

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The effects of cyclic stretch on gene transfer in alveolar epithelial cells
Taylor, W., Gokay, K. E., Capaccio, C., Davis, E., Glucksberg, M. R., & Dean, D. A. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(03)00041-8 · Cited by 31 · see citing works
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Authors: Geiger, R. C., Taylor, W., Glucksberg, M. R., & Dean, D. A.
Affiliations: Northwestern University (US)
Corresponding author: Dean, D A
ORCID: Glucksberg, M R
Dean, D A
Venue: Gene Therapy
Publisher: Springer Science and Business Media LLC
Published: 2006-01-26
Volume: 13
Issue: 8
Pages: 725-731
ISSN: 0969-7128 (ISSN-L)
1476-5462
DOI: 10.1038/sj.gt.3302693
PMC: PMC4150916
OpenAlex: W2074939226
Cited by: 64
References: 42
Citations by year: 2026: 4 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 9
FWCI: 2.07
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Gene Therapy (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Northwestern University
National Heart, Lung, and Blood Institute (HL 71643, P01HL071643, HL 076139, T32HL076139)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords: cyclic strain, cytoskeletal rearrangement, non-viral gene delivery, plasmid transfection, F-actin, microtubules, macromolecular diffusion, A549 cells, gene expression enhancement, mechanical stimulation
MeSH terms: Actins, Biological Transport, Cells, Cytoskeleton, Humans, Luciferases, Actin Cytoskeleton, Microscopy, Fluorescence, Microtubules, Stress, Mechanical, Tubulin, Genetic Therapy, Gene Expression, Electroporation, Cell Line, Tumor, Cell Size

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Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

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