nn8b06998_si_003.avi (147.37 kB)
Nanoneedle-Mediated Stimulation of Cell Mechanotransduction Machinery
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posted on 2019-03-04, 14:05 authored by 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. StevensBiomaterial
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.