Biology subjects

Zähringer, J.

Publications and source records attributed to Zähringer, J..

3 recordsLinked to original sources

bioRxiv2026

A Modular Framework for Automated Segmentation and Analysis of AFM Imaging of Chromatin Organization

Chromatin organization underlies essential genome functions, but its nanoscale organization remains challenging to capture and quantify with precision. Atomic force microscopy (AFM) offers direct structural readouts of DNA and chromatin, yet translating these rich images into reproducible biological metrics has been limited by the lack of standardized, scalable analysis tools. Here we present DNAsight, an automated analysis framework that integrates machine learning (ML)-based segmentation with modular, base-pair-calibrated quantification of DNA spatial organization, looping, nucleosome spacing, and protein clustering. Applied across diverse chromatin-associated proteins, DNAsight reveals protein-specific organizational signatures, including topology-dependent compaction by integration host factor (IHF), condition-dependent changes in loop-like DNA structures in cohesin-CTCF-precocious dissociation of sisters 5A (PDS5A) reactions, and promoter-driven multimerization of GAGA factor (GAF) clusters. The framework further enables direct extraction of nucleosome spacing distributions from raw AFM images, providing a label-free route to investigate chromatin fiber architecture. Together, these advances establish DNAsight as a generalizable and scalable approach for converting AFM measurements into quantitative insights into the physical principles of chromatin organization. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/708946v2_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1225883org.highwire.dtl.DTLVardef@1e1041dorg.highwire.dtl.DTLVardef@1d53d18org.highwire.dtl.DTLVardef@9e0a2a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Brownian DNA Computing

Conventional silicon computing is constrained by energy demands, limited parallelism, and poor compatibility with living systems, motivating the exploration of molecular alternatives. Here, we realize Brownian DNA computing, a hitherto theoretical framework, for energy efficient computation in which coupled molecular balances on a DNA origami scaffold form Brownian Logic Elements (BLEs) that harnesses thermal fluctuations for computation. By encoding multiple logic gates into a programmed energy landscape, these BLEs execute all fundamental Boolean logic gates, complex circuits such as half-adders, and multi-input operations, while also enabling non-Boolean logic with multi-valued outputs in a single compact gate. Computation arises through thermally driven exploration of a near-flat configurational energy landscape, without reliance on consumable fuel strands for cascading signal propagation, making the process fast, resettable, and compatible with operation near reversible thermodynamic limits. Transient-input protocols further allow the BLE energy landscape to be controlled quasistatically, providing a route toward reversible Brownian computation. In combination with single-molecule readout, Brownian DNA computing establishes a new foundation for molecular information processing with potential applications in biocomputing, soft robotics, and energy-efficient nanodevices.

biophysics↗

bioRxiv2020

Addressable Nanoantennas with Cleared Hotspots for Single-Molecule Detection on a Portable Smartphone Microscope

The advent of highly sensitive photodetectors1,2 and the development of photostabilization strategies3 made detecting the fluorescence of a single molecule a routine task in many labs around the world. However, to this day, this process requires cost-intensive optical instruments due to the truly nanoscopic signal of a single emitter. Simplifying single-molecule detection would enable many exciting applications, e.g. in point-of-care diagnostic settings, where costly equipment would be prohibitive.4 Here, we introduce addressable NanoAntennas with Cleared HOtSpots (NACHOS) that are scaffolded by DNA origami nanostructures and can be specifically tailored for the incorporation of bioassays. Single emitters placed in the NACHOS emit up to 461-fold brighter enabling their detection with a customary smartphone camera and an 8-US-dollar objective lens. To prove the applicability of our system, we built a portable, battery-powered smartphone microscope and successfully carried out an exemplary single-molecule detection assay for DNA specific to antibiotic-resistant Klebsiella pneumonia "on the road ".

biophysics↗