TY - JOUR T1 - A highly homogeneous expansion microscopy polymer composed of tetrahedron-like monomers JF - bioRxiv DO - 10.1101/814111 SP - 814111 AU - Ruixuan Gao AU - Chih-Chieh (Jay) Yu AU - Linyi Gao AU - Kiryl D Piatkevich AU - Rachael L Neve AU - Srigokul Upadhyayula AU - Edward S Boyden Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/10/22/814111.abstract N2 - Expansion microscopy (ExM) physically magnifies biological specimens to enable nanoscale-resolution imaging on conventional microscopes. Current ExM methods permeate biological specimens with free radical-polymerized polyacrylate hydrogels, whose network structure limits the microscopy resolution enabled by ExM. Here we report that ExM is possible using hydrogels with more homogeneous network structure, assembled via non-radical terminal linking of monomers of tetrahedral shape. 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 ~10x in linear dimension results in a viral envelope deviation from sphericity of 9.2 nm, rather than the 14.3 nm enabled by free radical-polymerized hydrogels used in earlier versions of ExM. Thus, tetra-gel polymer chemistry may support new forms of ExM imaging that introduce fewer spatial errors than earlier versions, and raise the question of whether single biomolecule precision may be achievable. ER -