Exploring arrays of vertical one-dimensional nanostructures for cellular investigations

Abstract

The endeavor of exploiting arrays of vertical one-dimensional (1D) nanostructures (NSs) for cellular applications has recently been experiencing a pronounced surge of activity. The interest is rooted in the intrinsic properties of high-aspect-ratio NSs. With a height comparable to a mammalian cell, and a diameter 100-1000 times smaller, NSs should intuitively reach far into a cell and, due to their small diameter, do so without compromising cell health. Single NSs would thus be expedient for measuring and modifying cell response. Further organization of these structures into arrays can provide up-scaled and detailed spatiotemporal information on cell activity, an achievement that would entail a massive leap forward in disease understanding and drug discovery. Numerous proofs-of-principle published recently have expanded the large toolbox that is currently being established in this rapidly advancing field of research. Encouragingly, despite the diversity of NS platforms and experimental conditions used thus far, general trends and conclusions from combining cells with NSs are beginning to crystallize. This review covers the broad spectrum of NS materials and dimensions used; the observed cellular responses with specific focus on adhesion, morphology, viability, proliferation, and migration; compares the different approaches used in the field to provide NSs with the often crucial cytosolic access; covers the progress toward biological applications; and finally, envisions the future of this technology. By maintaining the impressive rate and quality of recent progress, it is conceivable that the use of vertical 1D NSs may soon be established as a superior choice over other current techniques, with all the further benefits that may entail.

Tunable high aspect ratio polymer nanostructures for cell interfaces

“…High viability but somewhat reduced spreading area is consistent with earlier reports of cells on e.g. polystyrene nanopillars of similar dimensions as ours (although more densely spaced) 54 , and also general trends in studies of cells on other types of high aspect ratio nanostructures 6 .…”

“…Recently, there have been significant developments in biological applications of nanostructured surfaces, in particular high aspect ratio nanowires, nanopillars and nanotubes 6,7 . * In these systems, regular or randomly arranged nanostructures protrude vertically from a flat substrate.…”

Temporally resolved direct delivery of second messengers into cells using nanostraws

“…These cell penetrating structures have been shown to change certain cell behaviors and morphology without preventing migration or proliferation or altering transcription levels. [27][28][29] Here we demonstrate for the first time that cell-penetrating "nanostraws" provide direct, temporal control of a membrane-impermeant second messenger, Ca 2+ . The platform consists of 100 nm diameter hollow nanotubes that penetrate through the cell membrane with minimal perturbation, providing a long-term conduit into the cell cytoplasm ( Fig.…”

Micro- and Nanoscale Technologies for Delivery into Adherent Cells

“…The small size of the nanoprobe allows for extremely precise spatial positioning and long incubation times within the cell. The most common 1D nanostructures for nanoinjection are nanotubes and nanowires with dimensions of 1–750 nm in diameter and 0.5–20 µm in length assembled on a linear wire or cantilever support [32, 33]. Common nanoprobes are fabricated using carbon nanotubes [9], boron nitride nanotubes [4], and silicon nanowires [34].…”

“…Microfabricated substrates containing arrays of 1D nanostructures such as nanowires [22, 45–48] and nanostraws [24, 25] have been employed for delivery to and/or analysis of a population of adhered cells [33, 49]. When cells are cultured on top of the microfabricated substrates, the arrays of 1D nanostructures interact with the cells, although the exact mechanism of penetration of the cell membrane is currently being elucidated [50, 51].…”