Interfacing Cells with Vertical Nanoscale Devices: Applications and Characterization

Abstract

Measurements of the intracellular state of mammalian cells often require probes or molecules to breach the tightly regulated cell membrane. Mammalian cells have been shown to grow well on vertical nanoscale structures in vitro, going out of their way to reach and tightly wrap the structures. A great deal of research has taken advantage of this interaction to bring probes close to the interface or deliver molecules with increased efficiency or ease. In turn, techniques have been developed to characterize this interface. Here, we endeavor to survey this research with an emphasis on the interface as driven by cellular mechanisms.

High‐Aspect‐Ratio Nanostructured Surfaces as Biological Metamaterials

“…Throughout the literature, interactions are variously described as penetrating, piercing, perturbing, impaling, indenting, and mechanically disrupting the cell membrane, which reflects in part the lack of consensus over what is happening. In particular, many reports question whether the cell membrane is spontaneously penetrated by nanostructures, and this topic has been presented as a source of contention within the field. In this context, spontaneous penetration refers to a high‐aspect‐ratio nanostructure piercing the membrane of a cell that has been seeded onto a surface (with minimal applied external force).…”

“…Electron microscopy provides the most unambiguous visualization of the cell–nanostructure interface. Critical point drying and other dehydration procedures allow the shape and orientation of cells seeded on nanostructures to be imaged with high resolution, although care needs to be taken to preserve intracellular structures . Effective protocols facilitate high‐contrast imaging while minimizing fixation and vacuum artefacts that might artificially deform structures or alter cell–nanostructure distances .…”

“…Delivering molecules into cells enables intracellular sensing and control over cell behavior . Delivery efficiency depends on multiple factors, including cargo and cell type, and if done poorly can induce cell death . Exciting new gene, protein, and peptide therapies have the potential to tackle complex conditions, such as inherited human diseases, but rely upon the ability to simultaneously deliver biomolecules or transfect large numbers of cells in tissues, hence the demand for delivery technologies.…”

“…Immune cells are notoriously harder to transfect than most cell lines, but a desirable target for gene therapies . Shalek et al used silicon nanowires to deliver siRNA into a range of human and nonhuman primary immune cells .…”

“…The authors demonstrated their platform by monitoring the impact of ion‐channel blocking drugs on the beating behavior of the cardiac cells. Electroporation was required before intracellular signals were detected, as indicated by a significant improvement in the signal‐to‐noise ratio, and a shift from a bi‐ to monophasic waveform post‐electroporation . By tracking the signal intensity, researchers noted that the signal slowly reverts back to an extracellular waveform over the course of 10 min, suggesting that the intracellular interface is transient.…”