Engineered Nanotopographies Induce Transient Openings in the Nuclear Membrane

Materials with engineered nano-scale surface topographies, such as nanopillars, nanoneedles, and nanowires, mimic natural structures like viral spike proteins, enabling them to bypass biological barriers like the plasma membrane. These properties have led to applications in nanoelectronics for intracellular sensing and drug delivery platforms, some of which are already in clinical trials. Here, evidence is present that nanotopographic materials can induce transient openings in the nuclear membranes of various cell types without penetrating the cells, breaching the nucleo-cytoplasmic barrier, and allowing uncontrolled molecular exchange across the nuclear membrane. These openings, induced by nanoscale curvature, are temporary and repaired through the Endosomal Sorting Complexes Required for Transport (ESCRT)-mediated mechanisms. The findings suggest a potential for nano\topographic materials to temporarily breach the nuclear membrane with potential applications in direct nuclear sensing and delivery. This work reveals that nanotopographic materials can transiently breach the nucleo-cytoplasmic barrier by inducing nanoscale curvature in nuclear membranes. These breaches, occurring across various cell types, are influenced by the dimensions of nanopillars and the duration of cell interaction. The breaches are transient and repaired through the Endosomal Sorting Complexes Required for Transport(ESCRT)-mediated mechanisms. image