A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy

Expansion microscopy (ExM) physically magnifies biological specimens to enable nanoscale-resolution imaging using conventional microscopes. Current ExM methods permeate specimens with free-radical-chain-growth-polymerized polyacrylate hydrogels, whose network structure limits the local isotropy of e...

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Main Authors: Gao, Ruixuan, Yu, Chih-Chieh, Gao, Linyi, Piatkevich, Kiryl D, Neve, Rachael L, Munro, James B, Upadhyayula, Srigokul, Boyden, Edward S
Other Authors: McGovern Institute for Brain Research at MIT
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2021
Online Access:https://hdl.handle.net/1721.1/138170
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author Gao, Ruixuan
Yu, Chih-Chieh
Gao, Linyi
Piatkevich, Kiryl D
Neve, Rachael L
Munro, James B
Upadhyayula, Srigokul
Boyden, Edward S
author2 McGovern Institute for Brain Research at MIT
author_facet McGovern Institute for Brain Research at MIT
Gao, Ruixuan
Yu, Chih-Chieh
Gao, Linyi
Piatkevich, Kiryl D
Neve, Rachael L
Munro, James B
Upadhyayula, Srigokul
Boyden, Edward S
author_sort Gao, Ruixuan
collection MIT
description Expansion microscopy (ExM) physically magnifies biological specimens to enable nanoscale-resolution imaging using conventional microscopes. Current ExM methods permeate specimens with free-radical-chain-growth-polymerized polyacrylate hydrogels, whose network structure limits the local isotropy of expansion as well as the preservation of morphology and shape at the nanoscale. Here we report that ExM is possible using hydrogels that have a more homogeneous network structure, assembled via non-radical terminal linking of tetrahedral monomers. As with earlier forms of ExM, such 'tetra-gel'-embedded specimens can be iteratively expanded for greater physical magnification. Iterative tetra-gel expansion of herpes simplex virus type 1 (HSV-1) virions by ~10× in linear dimension results in a median spatial error of 9.2 nm for localizing the viral envelope layer, rather than 14.3 nm from earlier versions of ExM. Moreover, tetra-gel-based expansion better preserves the virion spherical shape. Thus, tetra-gels may support ExM with reduced spatial errors and improved local isotropy, pointing the way towards single-biomolecule accuracy ExM.
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spelling mit-1721.1/1381702023-06-22T13:52:33Z A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy Gao, Ruixuan Yu, Chih-Chieh Gao, Linyi Piatkevich, Kiryl D Neve, Rachael L Munro, James B Upadhyayula, Srigokul Boyden, Edward S McGovern Institute for Brain Research at MIT Program in Media Arts and Sciences (Massachusetts Institute of Technology) Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Center for Neurobiological Engineering Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Koch Institute for Integrative Cancer Research at MIT Howard Hughes Medical Institute Expansion microscopy (ExM) physically magnifies biological specimens to enable nanoscale-resolution imaging using conventional microscopes. Current ExM methods permeate specimens with free-radical-chain-growth-polymerized polyacrylate hydrogels, whose network structure limits the local isotropy of expansion as well as the preservation of morphology and shape at the nanoscale. Here we report that ExM is possible using hydrogels that have a more homogeneous network structure, assembled via non-radical terminal linking of tetrahedral monomers. As with earlier forms of ExM, such 'tetra-gel'-embedded specimens can be iteratively expanded for greater physical magnification. Iterative tetra-gel expansion of herpes simplex virus type 1 (HSV-1) virions by ~10× in linear dimension results in a median spatial error of 9.2 nm for localizing the viral envelope layer, rather than 14.3 nm from earlier versions of ExM. Moreover, tetra-gel-based expansion better preserves the virion spherical shape. Thus, tetra-gels may support ExM with reduced spatial errors and improved local isotropy, pointing the way towards single-biomolecule accuracy ExM. 2021-11-19T19:33:04Z 2021-11-19T19:33:04Z 2021 2021-11-19T19:28:43Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/138170 Gao, Ruixuan, Yu, Chih-Chieh, Gao, Linyi, Piatkevich, Kiryl D, Neve, Rachael L et al. 2021. "A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy." Nature Nanotechnology, 16 (6). en 10.1038/S41565-021-00875-7 Nature Nanotechnology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media LLC PMC
spellingShingle Gao, Ruixuan
Yu, Chih-Chieh
Gao, Linyi
Piatkevich, Kiryl D
Neve, Rachael L
Munro, James B
Upadhyayula, Srigokul
Boyden, Edward S
A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy
title A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy
title_full A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy
title_fullStr A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy
title_full_unstemmed A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy
title_short A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy
title_sort highly homogeneous polymer composed of tetrahedron like monomers for high isotropy expansion microscopy
url https://hdl.handle.net/1721.1/138170
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