Biology subjects

Mohr, J. M.

Publications and source records attributed to Mohr, J. M..

3 recordsLinked to original sources

bioRxiv2026

Nanoscale Organization of Membrane Tension during Neutrophil Extracellular Trap Formation Revealed by Fluorescence Lifetime Imaging

Cells continuously generate and respond to mechanical forces across compartments, with the plasma membrane acting as a nanoscale interface for sensing and transmitting tension. How intracellular forces are translated into membrane tension during dynamic processes such as neutrophil extracellular trap (NET) formation remains unclear. Here, we combine the mechanosensitive fluorescent probe Flipper-TR with fluorescence lifetime imaging microscopy (FLIM) to map spatiotemporal changes in plasma membrane tension in living cells. After validation in HeLa and dHL-60 cells under osmotic perturbation, we apply this approach to primary human neutrophils undergoing NETosis. Membrane tension transiently increases during chromatin decondensation and nuclear swelling within 90 min and is followed by a marked decrease 30 min after membrane rupture. Prior to rupture, tension is spatially heterogeneous, indicating localized nanoscale mechanical regulation. Cholesterol depletion abolishes the transient increase and reduces heterogeneity without affecting overall NETosis kinetics. Together, these findings establish the plasma membrane as a dynamic nanoscale reporter of intracellular mechanical stress during NETosis.

immunology↗

bioRxiv2026

Simulation of neurotransmitter release and its imaging by fluorescent sensors

Cells release signaling molecules such as neurotransmitters that diffuse through the extracellular space and bind to receptors. These signaling molecules can be detected by fluorescent sensors/probes to provide images of the signaling process. Such images are not equivalent to a concentration because diffusion and sensor kinetics affect (convolute) them. Therefore, computational approaches are necessary to disentangle these contributions and allow interpretation of fluorescent sensor-based images. Here, we present a kinetic Monte Carlo framework (FLuorescence Imaging Kinetic Simulation, FLIKS) that simulates signaling molecules undergoing cellular release, stochastic diffusion and reversible binding to sensors in realistic cellular (2D or 3D) geometries. We apply it to model neurotransmitter (dopamine) release in synaptic clefts and for paracrine signaling by immune cells. We also show how sensor location, sensor kinetics and release location affect fluorescence images. For example, we show how sensor sensitivity depends on the distance from the synaptic cleft and changes when dopamine transporters (DAT) clear dopamine. The approach also allows to compare the performance of membrane bound (genetically encoded) sensors versus artificial sensors such as nanosensors placed outside under or around the cells. As an example, we also demonstrate how the images of catecholamine release by immune cells can be modeled and compared to experimental data to better understand the release pattern. This framework provides a quantitative basis for analyzing and interpreting fluorescent sensor imaging data.

neuroscience↗

bioRxiv2025

Rapid catecholamine trafficking regulates neutrophil functions and neutrophil-platelet interactions

Neutrophils are key effector cells of the innate immune system that respond to small signaling molecules regulating immune responses. For a long time, similarities between neuronal and immune cells have been discussed. Here, we show that human neutrophils rapidly take up, package and use catecholamine neurotransmitters such as dopamine or epinephrine via the machinery known from neurons. Uptake and release of catecholamines as well as trafficking and packaging into MPO/VMAT2-positive primary vesicles is visualized with false fluorescent neurotransmitters. We also directly image the fast (> 10 s) and transient release of catecholamines from neutrophils with near infrared fluorescent nanosensors. Serotonin or activated platelets trigger calcium (Ca2+) signaling and consequently exocytosis of catecholamines. They reduce NET-formation but increase platelet aggregation. Thus, we establish similarities between neurons and neutrophils and identify a paracrine neutrophil-platelet feedback loop relevant for inflammatory and coagulatory conditions.

immunology↗