Biology subjects

Dahlberg, S. K.

Publications and source records attributed to Dahlberg, S. K..

3 recordsLinked to original sources

bioRxiv2026

Resolving multivalent antibody binding states with defined spatial antigen-patterning

Multivalent interactions are fundamental to many biological systems, including how antibodies bind to their respective antigens. Still, their accumulated binding strength, i.e. avidity, resulting from binding and rebinding events of multiple interacting points, remains difficult to measure. Classical assay platforms like ELISA and SPR lack control over antigen positioning, limiting the resolution of the binding characteristics that shape biological outcomes at nanoscale. Here, we present PANMAP, a planar and plate-based assay inspired by ELISA that uses DNA origami to present antigens at defined nanoscale patterns, enabling direct measurements of spatially resolved binding events, termed avidity profiles. Using IgG antibodies as a model system, PANMAP distinguishes between monovalent and bivalent binding states by combining equilibrium absorbance measurements with a simple biophysical model. The avidity profiles reveal how the balance shifts between monovalent and bivalent interactions as a function of antibody concentration and antigen spacing, with intermediate separation distances favoring bivalent binding events and excluded at both near and far distances. This spatial profiling allows decoupling of affinity dependency from avidity profiles to reveal how spatial constraints influence binding equilibria. Our approach fills a longstanding gap in multivalent interaction measurement and offers a new tool for antibody engineering, development of multivalent reagents, therapeutic screening, and mechanistic immunology.

immunology↗

bioRxiv2024

Hidden network preserved in Slide-tags data allows reference-free spatial reconstruction

Spatial transcriptomics technologies aim to spatially map gene expression in tissues and typically use oligonucleotide array surfaces that have undergone spatial indexing. These arrays are used to capture nucleic acids diffusing from adjacently placed tissues, allowing subsequent sequencing to reveal both gene and position. Slide-tags is a recently developed method by Russell et al. that inverts this principle. Instead of capturing molecules released from the tissue, probes are detached from a pre-decoded bead array and diffused into tissues, tagging nuclei with spatial barcodes. We reanalyzed this data and discovered a latent, spatially informative cell-bead network formed incidentally from barcode diffusion and the biophysical properties of the tissue. This allows us to treat Slide-tags as a new network-based imaging-by-sequencing approach. By optimizing spatial constraints encoded in the cell-bead network structure, we could achieve unassisted tissue reconstruction, a fundamental shift from classical spatial technologies based on pre-indexed arrays.

bioinformatics↗

bioRxiv2024

Spatial Coherence of DNA Barcode Networks

Sequencing-based microscopy is a novel, optics-free method for imaging molecules in biological samples using molecular DNA barcodes, spatial networks, and sequencing technologies. Despite its promise, the principles determining how these networks preserve spatial information are not fully understood. Current validation methods, which rely on comparing reconstructed positions to expected results, would benefit from a deeper understanding of these principles. Here, we introduce the concept of spatial coherence-- a set of fundamental properties of spatial networks that quantifies the alignment between topological relationships and Euclidean geometry. Our findings show that spatial coherence is an effective method for evaluating a networks capacity to maintain spatial fidelity and identify distortions, independent of prior information. This framework provides a cost-effective validation tool for sequencing-based microscopy by taking advantage of the fundamental properties of spatial networks in nanoscale systems.

bioinformatics↗