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Abstract The function of neuronal circuits, and its perturbation by psychoactive molecules or disease-associated genetic variants, is governed by the interplay between synapse activity and synaptic protein localization and synthesis across a heterogeneous synapse population. Here, we combine in situ measurement of synaptic multiprotein compositions and activation states, synapse activity in calcium traces or glutamate spiking, and local translation of specific genes, across the same individual synapses. We demonstrate how this high-dimensional data enables identification of interdependencies in the multiprotein-activity network, and causal dissection of complex synaptic phenotypes in disease-relevant chemical and genetic NMDAR loss of function that translatein vivo. We show how this method generalizes to other subcellular systems by deriving mitochondrial protein networks, and, using support vector machines, its value in overcoming animal variability in phenotyping. Integrating multiple synapse information modalities enables deep structure-function characterization of synapse populations and their responses to genetic and chemical perturbations. 

Abstract Incorporation of colloidal quantum emitters into silicon-based photonic devices would enable major advances in quantum optics. However, deterministic placement of individual sub-10 nm colloidal particles onto micron-sized photonic structures with nanometer-scale precision remains an outstanding challenge. Here, we introduce Cavity-Shape Modulated Origami Placement (CSMOP) that leverages the structural programmability of DNA origami to precisely deposit colloidal nanomaterials within lithographically-defined resist cavities. CSMOP enables clean and accurate patterning of origami templates onto photonic chips with high yields. Soft-silicification-passivation stabilizes deposited origamis, while preserving their binding sites to attach and align colloidal quantum rods (QRs) to control their nanoscale positions and emission polarization. We demonstrate QR integration with photonic device structures including waveguides, micro-ring resonators, and bullseye photonic cavities. CSMOP therefore offers a general platform for the integration of colloidal quantum materials into photonic circuits, with broad potential to empower quantum science and technology. 

DNA nanotechnology has broad applications in biomedical drug delivery and pro- grammable materials. Characterization of the self-assembly of DNA origami and quan- tum dots (QDs) is necessary for the development of new DNA-based nanostructures. We use computation and experiment to show that the self-assembly of 3D hierarchi- cal nanostructures can be controlled by programming the binding site number and their positions on DNA origami. Using biotinylated pentagonal pyramid wireframe DNA origamis and streptavidin capped QDs, we demonstrate that DNA origami with 1 binding site at the outer vertex can assemble multi-meric origamis with up to 6 DNA origamis on 1 QD, and DNA origami with 1 binding site at the inner center can only assemble monomeric and dimeric origamis. Meanwhile, the yield percentages of differ- ent multi-meric origamis are controlled by the QD:DNA-origami stoichiometric mixing ratio. DNA origamis with 2 binding sites at the αγ positions (of the pentagon) make larger nanostructures than those with binding sites at the αβ positions. In general, increasing the number of binding sites leads to increases in the nanostructure size. At high DNA origami concentration, the QD number in each cluster becomes the limiting factor for the growth of nanostructures. We find that reducing the QD size can also affect the self-assembly because of the reduced access to the binding sites from more densely packed origamis. 

Scalable fabrication of two-dimensional (2D) arrays of quantum dots (QDs) and quantum rods (QRs) with nanoscale precision is required for numerous device applications. However, self-assembly–based fabrication of such arrays using DNA origami typically suffers from low yield due to inefficient QD and QR DNA functionalization. In addition, it is challenging to organize solution-assembled DNA origami arrays on 2D device substrates while maintaining their structural fidelity. Here, we reduced manufacturing time from a few days to a few minutes by preparing high-density DNA-conjugated QDs/QRs from organic solution using a dehydration and rehydration process. We used a surface-assisted large-scale assembly (SALSA) method to construct 2D origami lattices directly on solid substrates to template QD and QR 2D arrays with orientational control, with overall loading yields exceeding 90%. Our fabrication approach enables the scalable, high fidelity manufacturing of 2D addressable QDs and QRs with nanoscale orientational and spacing control for functional 2D photonic devices. 

The complex functions of neuronal synapses depend on their tightly interconnected protein network, and their dysregulation is implicated in the pathogenesis of autism spectrum disorders and schizophrenia. However, it remains unclear how synaptic molecular networks are altered biochemically in these disorders. Here, we apply multiplexed imaging to probe the effects of RNAi knockdown of 16 autism- and schizophrenia-associated genes on the simultaneous joint distribution of 10 synaptic proteins, observing several protein composition phenotypes associated with these risk genes. We apply Bayesian network analysis to infer hierarchical dependencies among eight excitatory synaptic proteins, yielding predictive relationships that can only be accessed with single-synapse, multiprotein measurements performed simultaneously in situ. Finally, we find that central features of the network are affected similarly across several distinct gene knockdowns. These results offer insight into the convergent molecular etiology of these widespread disorders and provide a general framework to probe subcellular molecular networks. 

Abstract Functionalization of quantum dots (QDs) and quantum rods (QRs) with ligands is essential for their further practical application across various domains. Dehydration‐assisted functionalization (DAF) is a versatile method applicable to a wide range of hydrophilic ligands with an affinity to the surface of QDs and QRs. This approach facilitates rapid one‐pot ligand exchange and dense modification by efficiently transferring these ligands onto the surface of QDs and QRs. This study demonstrates the efficacy of DAF in preparing chiral QRs, engineering the surface charge of QDs, utilizing QR aggregates, and conjugating dense DNA onto cadmium‐free InP/ZnS QDs. DAF therefore offers a versatile solution for hydrophilic ligand functionalization of QDs and QRs applicable to diverse applications.