Biology subjects

Dean, W. F.

Publications and source records attributed to Dean, W. F..

3 recordsLinked to original sources

bioRxiv2026

The Desmoplakin Hinge Domain Confers a Reversible Conformational Change in Response to Acute External Force

Desmosomes provide mechanical integrity to tissues that experience strain, yet how mechanical force is sensed and distributed within the desmosomal plaque remains poorly understood. Here we identify the hinge within the desmoplakin (DP) head domain is required for repositioning the DP tail in response to acute uniaxial mechanical stretch. This repositioning occurs within 30 seconds of applied stretch and reverses with release, indicating a dynamic reversible switch rather than a stable structural transition. We show this hinge-dependent repositioning correlates with the propagation of mechanical force to the desmosomal cadherins, consistent with the hinge's role in buffering tension at the cadherin interface during mechanical loading. Deletion or shortening of the hinge abolishes the stretch-induced response and compromises desmosome mechanical integrity. The repositioning of the DP tail in the calcium-dependent to hyper-adhesive transition was not impacted by alterations to the hinge, demonstrating that DP repositioning due to acute force or adhesive state is mechanistically distinct. Together, these findings define a reversible, hinge-dependent mechanotransduction pathway through which DP senses and relays mechanical force within the desmosome. This mechanism could act as a mechanical buffer by reducing the impulse of forces on the cadherins, and play a central role in mechanical resilience.

cell biology↗

bioRxiv2026

N-cadherin orientational order decreases with mechanical load at cardiomyocyte adherens junctions

Adherens junctions physically connect neighboring cells and are built around classical cadherins, homophilic transmembrane proteins that link to the actin cytoskeleton. Classical cadherins can organize into ordered arrays in vitro, but whether they do so in cells remains to be established. Here, we use fluorescence polarization microscopy to show that the classical cadherin N-cadherin is orientationally ordered at cardiomyocyte cell-cell junctions. Whereas the desmosomal cadherin desmoglein 2 was similarly ordered across junction types, N-cadherin order was spatially heterogeneous. Order was lowest where organized myofibrils terminate at high-load, vinculin-enriched axial junctions and highest at low-load, vinculin-poor lateral junctions. This inverse relationship between order and mechanical load suggests that robust cadherin-mediated adhesion does not require ectodomain order. Our findings provide evidence that a classical cadherin is orientationally ordered in cells and show that mechanically active adhesions adopt distinct organizational strategies according to local mechanical demands. Summary StatementAt cardiomyocyte junctions, N-cadherin is ordered where mechanical load is low but disordered where load is high, suggesting that cadherin organization adapts to local force conditions.

cell biology↗

bioRxiv2023

OOPS: Object-Oriented Polarization Software for analysis of fluorescence polarization microscopy images

Most essential cellular functions are performed by proteins assembled into larger complexes. Fluorescence Polarization Microscopy (FPM) is a powerful technique that goes beyond traditional imaging methods by allowing researchers to measure not only the localization of proteins within cells, but also their orientation or alignment within complexes or cellular structures. FPM can be easily integrated into standard widefield microscopes with the addition of a polarization modulator. However, the extensive image processing and analysis required to interpret the data have limited its widespread adoption. To overcome these challenges and enhance accessibility, we introduce OOPS (Object-Oriented Polarization Software), a MATLAB-based analysis tool tailored for FPM data. This work highlights the distinctive features of our software, which empower researchers to efficiently manage large datasets; detect and analyze individual structures; conduct population assessments based on morphology, intensity, and polarization-specific parameters; and create publication-quality visualizations, all within a user-friendly graphical interface. Importantly, OOPS is adaptable to various sample types, labeling techniques, and imaging setups, facilitating in-depth analysis of diverse polarization-sensitive samples. Here, we demonstrate the power and versatility of our approach by applying OOPS to FPM images of both punctate and filamentous structures. OOPS is freely available under the GNU GPL 3.0 license and can be downloaded at https://github.com/Mattheyses-Lab/OOPS.

cell biology↗