Expansion Microscopy: Toward Nanoscale Imaging of a Diverse Range of Biomolecules.

Abstract

Expansion microscopy (ExM) has become a powerful imaging tool for visualizing the nanoscale organization of protein and nucleic acid targets in cells and tissues using only a conventional microscope. Until recently, current ExM approaches have had limited applicability to imaging other biomolecules, such as lipids and small molecules. With the new TRITON probes reported by Wen <i>et al.</i> in this issue of <i>ACS Nano</i>, ExM can now be used to perform nanoscale imaging of the cytoskeleton and lipid membranes. In this Perspective, we offer a brief overview of recent developments in ExM, with a focus on biomolecule anchoring and labeling strategies that target a wide range of biomolecules to the water-swellable polymer formed <i>in situ</i>, a key step that ensures biomolecules or labels of interest are separated in space and can be resolved on a conventional microscope. In addition to these new advancements, we discuss challenges and future directions in this exciting field.