Publications

Authors: Verena Dobretzberger, Alexander Hebel, Maria Ponetsmüller, Florian Ohner, Trishant R. Umrekar, Morgan Beeby, Friedrich C. Simmel, Ivan Barišić

Journal: Small Structures

Published: 2 February 2026

DOI: https://doi.org/10.1002/sstr.202500864

Abstract:
Previous studies have shown that DNA origamis assembled from gene-encoding scaffolds can be taken up by mammalian cells and ultimately lead to the expression of the encoded genes. While interactions of DNA origami structures with mammalian cells have been extensively investigated, their interactions with bacteria remain poorly understood. Here, we systematically study how structure, folding state, chemical functionalization, and polycationic coatings influence the uptake and expression of gene-encoding DNA origami structures in E. coli. Using complementary positive- and negative selection assays, we show that DNA origami structures display markedly lower transformation efficiencies than their corresponding circular single-stranded scaffolds. Folding geometry, compactness, and scaffold accessibility strongly modulate transformation, with partially folded origami structures showing considerably higher activity. Chemical functionalization did not improve uptake, whereas polyplex formation can improve stability and transformation. Fluorescence and electron microscopy reveal that DNA origami structures predominantly associate with the bacterial surface. Leveraging the intrinsically low transformability of intact DNA origamis, we engineered photocleavable nanostructures that enable UV-triggered release of gene-encoding scaffolds, providing switchable activation of transformation. Our results offer fundamental insights into the bacterial processing of DNA nanostructures and establish a framework for controlling DNA entry and expression using programmable nanoscale carriers.

Authors: Louis Givelet, Sophie von Schönberg, Florian Katzmeier & Friedrich C. Simmel

Journal: Nature communications

Published: 28 April 2026

DOI: https://doi.org/10.1002/sstr.202500864

Abstract:
Since their discovery, bacteriophages—viruses that infect bacteria—have been invaluable to molecular biology and biotechnology. Renewed interest in phage-based antimicrobials, driven by the global antibiotic resistance crisis, highlights the need for improved quantitative tools. While conventional double-layer plaque assays (DLA) have provided foundational insights, they are limited by their inability to monitor infection dynamics over time and the inflexibility in experimental setups. Here, we present a high-throughput droplet microfluidics platform to quantify individual phage infection events. By co-encapsulating individual phages and bacteria in microfluidic droplets, we precisely control key experimental parameters such as exposure time and the ratio of phages to bacteria. This approach enables direct quantification of lysis events and measurement of lysis kinetics without interference from further progeny-driven infection processes inherent to bulk cultures. Applicable to diverse phage-host systems, this method offers a dynamic and accurate framework for studying phage biology and supports the development of phage-based antimicrobial strategies.