Biology subjects

Hogberg, B.

Publications and source records attributed to Hogberg, B..

4 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↗

bioRxiv2023

An error correction strategy for image reconstruction by DNA sequencing microscopy

By pairing adjacent molecules in-situ and then mapping these pairs, DNA microscopy could significantly reduce workload in spatial omics methods by directly inferring geometry from sequencing data alone. However, experimental artefacts can lead to errors in the adjacency data which distort the spatial reconstruction. Here, we describe a method to correct two such errors: spurious crosslinks formed between any two nodes, and fused nodes that are formed out of multiple molecules. We build on the principle that spatially close molecules should be connected and show that these errors violate this principle, allowing for their detection and correction. Our method corrects errors in simulated data, even in the presence of up to 20% errors, and proves to be more efficient at removing errors from experimental data than a read count filter. Integrating this method in DNA microscopy will significantly improve the accuracy of spatial reconstructions with lower data loss.

bioinformatics↗

bioRxiv2021

Nanoengineered DNA origami with repurposed TOP1 inhibitors targeting myeloid cells for the mitigation of neuroinflammation

Targeting myeloid cells, especially microglia, for the treatment of neuroinflammatory diseases such as multiple sclerosis (MS), is underappreciated. Here, we screened a library of compounds and identified the topoisomerase 1 (TOP1) inhibitor camptothecin (CPT) as a promising drug candidate for microglial modulation. CPT and its FDA-approved analog topotecan (TPT) inhibited inflammatory responses in microglia and macrophages, and ameliorated neuroinflammation in mice. Transcriptomic analysis of sorted microglia revealed an altered transcriptional phenotype following TPT treatment, with Ikzf1 identified as a potential target. Importantly, TOP1 expression was found elevated in several neuroinflammatory conditions, including human MS brains. To achieve targeted delivery to myeloid cells we designed a nanosystem using DNA origami and loaded TPT into it (TopoGami). TopoGami also significantly suppressed the inflammatory response in microglia and mitigated disease progression in MS-like mice. Our findings suggest that TOP1 inhibition represents a therapeutic strategy for neuroinflammatory diseases, and the proposed nanosystem may foster future research and drug development with a demand to target myeloid cells.

immunology↗

bioRxiv2019

A DNA nanoassembly-based approach to map membrane protein nanoenvironments

Super-resolution imaging has revealed that most proteins at the plasma membrane are not uniformly distributed but localize to dynamic domains of nanoscale dimensions. To investigate their functional relevance, there is a need for methods that enable comprehensive mapping of the compositions and spatial organizations of membrane protein nanodomains in cell populations. However, current superresolution methods are limited to analysing small, preselected subsets of proteins, at very low sampling fractions. Here we describe the development of a non-microscopy based super-resolution method for unbiased ensemble analysis of membrane protein nanodomains. The method, termed NANOscale DEciphEring of membrane Protein nanodomains (NanoDeep), is based on the use of DNA nanoassemblies to translate membrane protein organization information into a DNA sequencing readout. Using NanoDeep, we characterized the nanoenvironments of Her2, a membrane receptor of critical relevance in cancer. We found that the occupancies of Her2, Her3 and EGFR in the nanoenvironments surrounding Her2 were similar in two cell lines with vastly different expression levels of Her2. Further, we found that adding Heregulin-{beta}1 to cancer cells led to increased occupancy of Her2 and Her3, and to a lesser extent EGFR, in Her2 nanoenvironments. NanoDeep has the potential to provide new insights into the roles of the composition and spatial organization of protein nanoenvironments in the regulation of membrane protein function.

bioengineering↗