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SUMMARY:Stable Yet Specific: Designing a Gold Nanocluster CryoEM Label
LOCATION:Chemistry A101
TZID:America/Denver
DTSTART:20260501T160000
UID:2026-05-07-00-20-24@natsci.colostate.edu
DTSTAMP:20260507T002024
Description:While cryo-electron microscopy (cryoEM) has progressed towards 
 imaging cells in near-native states\, effective labeling of biomolecules r
 emains a major bottleneck. The intracellular environment is highly complex
 \, driving non-specific interactions and label-associated perturbations th
 at hinder accurate biomacromolecule localization.\nAn ideal cryoEM label m
 ust provide easy visibility and selective target binding. Colloidal gold n
 anoparticle (AuNPs) labels are widely used due to their strong electron co
 ntrast and tunable surface chemistry\, but suffer from non-specific and no
 n-stoichiometric labeling\, size dispersity\, and susceptibility to ligand
  exchange in intracellular environments.\n\nAtomically precise gold nanocl
 usters (AuNCs) have emerged as promising alternatives due to their monodis
 persity and well-defined ligand shells. NanogoldTM (a 1.4 nm Au55NC) is a
  common\, commercially available label\, but evidence suggests its ligand 
 shell—likely composed of triphenylphosphine (PPh3​) —is prone to exc
 hange with intracellular thiols such as glutathione. This instability can 
 result in aggregation\, protein corona formation\, and disruption of nativ
 e cellular conditions\, highlighting the need for more robust and specific
  AuNC-based labels.\n\nThis proposal aims to develop a next-generation AuN
 C cryoEM label that simultaneously enhances ligand exchange resistance and
  target specificity. The design leverages a water-soluble\, para-mercaptob
 enzoic acid (pMBA)-protected AuNC scaffold modified with a mixed ligand sh
 ell. This ligand shell incorporates a stealth component (e.g.\, polysarcos
 ine) to minimize non-specific interactions\, alongside a biomolecular anch
 or to enable selective targeting. Ligand exchange resistance will be evalu
 ated using a two-dimensional titration framework\, probing AuNC stability 
 under increasing glutathione concentrations and varying ionic and protein 
 conditions representative of biological environments. Target specificity w
 ill be assessed using ribosomal labeling as a proof of concept. Functional
 ized AuNCs will be incubated in mixtures containing ribosomes and competin
 g biomacromolecules\, and transmission electron microscopy (TEM) will be u
 sed to quantify labeling selectivity and assess any structural or morpholo
 gical changes in the AuNCs.\n\nOverall\, this work seeks to establish a de
 sign framework for stable\, specific AuNC-based labels that enable more ac
 curate and minimally perturbative intracellular cryoEM imaging. 4:00 pm
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