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Nanoneedle-mediated stimulation of cell mechanotransduction machinery

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Title: Nanoneedle-mediated stimulation of cell mechanotransduction machinery
Authors: Hansel, C
Crowder, S
Cooper, S
Gopal, S
Pardelha da Cruz, J
De Oliveira Martins, L
Keller, D
Rothery, S
Becce, M
Cass, A
Bakal, C
Chiappini, C
Stevens, M
Item Type: Journal Article
Abstract: Biomaterial substrates can be engineered to present topographical signals to cells which, through interactions between the material and active components of the cell membrane, regulate key cellular processes and guide cell fate decisions. However, targeting mechanoresponsive elements that reside within the intracellular domain is a concept that has only recently emerged. Here, we show that mesoporous silicon nanoneedle arrays interact simultaneously with the cell membrane, cytoskeleton, and nucleus of primary human cells, generating distinct responses at each of these cellular compartments. Specifically, nanoneedles inhibit focal adhesion maturation at the membrane, reduce tension in the cytoskeleton, and lead to remodeling of the nuclear envelope at sites of impingement. The combined changes in actin cytoskeleton assembly, expression and segregation of the nuclear lamina, and localization of Yes-associated protein (YAP) correlate differently from what is canonically observed upon stimulation at the cell membrane, revealing that biophysical cues directed to the intracellular space can generate heretofore unobserved mechanosensory responses. These findings highlight the ability of nanoneedles to study and direct the phenotype of large cell populations simultaneously, through biophysical interactions with multiple mechanoresponsive components.
Issue Date: 26-Mar-2019
Date of Acceptance: 21-Feb-2019
URI: http://hdl.handle.net/10044/1/68052
DOI: https://dx.doi.org/10.1021/acsnano.8b06998
ISSN: 1936-0851
Publisher: American Chemical Society
Start Page: 2913
End Page: 2019
Journal / Book Title: ACS Nano
Volume: 13
Issue: 3
Copyright Statement: © 2019 American Chemical Society. ACS AuthorChoice - This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Sponsor/Funder: Commission of the European Communities
Biotechnology and Biological Sciences Research Council (BBSRC)
Engineering & Physical Science Research Council (EPSRC)
Wellcome Trust
Commission of the European Communities
Commission of the European Communities
Funder's Grant Number: 301445
BB/L015129/1
EP/K020641/1
098411/Z/12/Z
ERC-2013-CoG-616417
655698
Keywords: cell−material interactions
mechanotransduction
nanoneedles
nuclear mechanics
porous silicon
super-resolution microscopy
MD Multidisciplinary
Nanoscience & Nanotechnology
Publication Status: Published
Online Publication Date: 2019-03-04
Appears in Collections:Faculty of Engineering
Materials
Chemistry
Biological and Biophysical Chemistry
National Heart and Lung Institute
Faculty of Medicine
Faculty of Natural Sciences



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