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
