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Nanoneedle-Mediated Stimulation of Cell Mechanotransduction Machinery

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Catherine S. Hansel, Spencer W. Crowder, Samuel Cooper, Sahana Gopal, Maria João Pardelha Da Cruz, Leonardo De Oliveira Martins, Debora Keller, Stephen Rothery, Michele Becce, Anthony E. G. Cass, Chris Bakal, Ciro Chiappini, Molly M. Stevens

Original languageEnglish
Pages (from-to)2913-2926
Number of pages14
JournalACS Nano
Volume13
Issue number3
Early online date4 Mar 2019
DOIs
Publication statusPublished - 26 Mar 2019

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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.

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