Materials patterned with high-aspect-ratio nanostructures have features on similar lengthscales to cellular components. These surfaces are an extreme topography on the cellular level
and have become useful tools for perturbing and sensing the cellular environment. Motivation
comes from the ability of high-aspect-ratio nanostructures to deliver cargoes into cells and
tissues, access the intracellular environment, and control cell behavior. These structures
directly perturb cells’ ability to sense and respond to external forces, influencing cell fate and
enabling new mechanistic studies. Through careful design of their nanoscale structure, these
systems act as biological metamaterials, eliciting unusual biological responses. While
predominantly used to interface eukaryotic cells, there is growing interest in non-animal and
prokaryotic cell interfacing. Both experimental and theoretical studies have attempted to
develop a mechanistic understanding for the observed behaviors, predominantly focusing on
the cell – nanostructure interface. Here, we consider how high-aspect-ratio nanostructured
surfaces are used to both stimulate and sense biological systems and discuss remaining
research questions.