Engineered Nanotopographies Induce Transient Openings in the Nuclear Membrane

Author:

Sarikhani Einollah1ORCID,Patel Vrund1,Li Zhi2,Meganathan Dhivya Pushpa1,Rahmani Keivan1ORCID,Sadr Leah1,Hosseini Ryan1,Visda Diether1,Shukla Shivani2,Naghsh‐Nilchi Hamed1ORCID,Balaji Adarsh3ORCID,McMahon Gillian34ORCID,Chen Shaoming1,Schöneberg Johannes34ORCID,McHugh Colleen A.3ORCID,Shi Lingyan2ORCID,Jahed Zeinab12ORCID

Affiliation:

1. Aiiso Yufeng Li Family Department of Chemical and Nano Engineering University of California San Diego La Jolla San Diego CA 92093 USA

2. Shu Chien‐Gene Lay Department of Bioengineering University of California San Diego La Jolla San Diego CA 92093 USA

3. Department of Chemistry and Biochemistry University of California San Diego La Jolla San Diego CA 92093 USA

4. Department of Pharmacology University of California La Jolla San Diego CA 92093 USA

Abstract

AbstractMaterials 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.

Funder

National Science Foundation

Cancer Research Coordinating Committee

National Institute of Diabetes and Digestive and Kidney Diseases

Air Force Office of Scientific Research

Publisher

Wiley

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