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Biology subjects

Wuerthner, L.

Publications and source records attributed to Wuerthner, L..

3 recordsLinked to original sources

phyB photobodies display molecular memory, regulating light signaling transcriptional states through phase separation.

Phytochrome B is a crucial red and far-red light sensor, which controls plant development and environmental responses to light and temperature. In the nucleus, phyB forms phase separated condensates, also called photobodies, consisting of various transcriptional regulators and transcription factors. phyB photobodies can form or disperse depending on the amount of light, the light quality, or ambient temperature. However, the biological relevance for forming photobodies is still unclear. In recent years the study of condensates has given rise to the idea that condensates can act as molecular memory, either due to long equilibration timescales arising from strong interactions can kinetically trap a mixture in a phase-separated state beyond the equilibrium coexistence line, or from phase-separation dependent modification processes or transcriptional regulation. Here, we hypothesize that the formation of phyB photobodies and the associated sequestration of signaling molecules allows for the formation of cell-type specific memory about light conditions. To address this hypothesis, we first developed a live imaging setup of phyB photobodies which shows that they do not follow classic liquid-liquid phase separation dynamics, but instead have a restriction on their size, intensity and minimum number. Fluorescence recovery after photobleaching (FRAP) then showed that photobodies between cell types have different levels of mobilities and diffusivities, suggesting that they are more stable in darkness or high red light, versus low red light. These differences in phyB photobody stability between cell types were also confirmed through whole-mount confocal imaging and single-nucleus transcriptomics in the same light-perturbation series. Through sci-Seq single nucleus spatial transcriptomics of the cotyledon in this light perturbation series, we identify a photobody-associated transcriptional cluster of nuclei that regulates photosynthesis, circadian rhythm, and RNA processing; the phyB photobody likely promotes its own stability by regulating TZP and PCH1 expression. The correlation between photobodies and transcriptional regulation shows how phyB condensates can provide cell-type specific light responses and exhibit signaling memory in changing environmental conditions.

cell biology↗

Geometry of disordered porous environments regulates cell migration

Cell migration is a dynamic process that is of critical importance to various aspects of living organisms, including organogenesis, wound healing, and immune responses. Several external factors are known to influence and direct active cell movement, such as chemokine gradients or the composition and mechanical properties of the extracellular matrix (ECM). While progress has been made in elucidating some of the biochemical pathways that control cell migration, little is known about the impact of the porous structure of the ECM on active cell motion. Here, by combining computational modelling and theory, we reveal how porous environments, as represented by the ECM, determine cell migration dynamics. Simulating cell movement in a 3D cellular Potts model accounting for amoeboid-like cell shape dynamics, we show that cell migration within disordered porous environments is characterized by distinct transient motility regimes that deviate from persistent motion and are best described by hopping of cells between traps. Using theory, we are able to show how these motility regimes and large scale transport properties are linked to geometrical properties of the microstructure. Importantly, our analyses reveal that spatial heterogeneities in the porosity lead to non-homogeneous cell distributions and effectively guide cell movement towards regions of low porosity, an effect which we here term as porotaxis. Overall, our work reveals the porosity of the ECM as an important control parameter that shapes cell migration and cellular distribution, and provides a conceptual framework to relate experimentally observed cell motility modes to tissue structures and vice versa. This connection between geometry and cell motility could enhance our understanding of how structural elements shape cell migration and tissue organization in various conditions, such as chronic inflammation, immunity, and cancer.

biophysics↗

Dynamics of the Bacillus subtilis Min system

Division site selection is a vital process to ensure generation of viable offspring. In many rod-shaped bacteria a dynamic protein system, termed the Min system, acts as a central regulator of division site placement. The Min system is best studied in Escherichia coli where it shows a remarkable oscillation from pole to pole with a time-averaged density minimum at midcell. Several components of the Min system are conserved in the Gram-positive model organism Bacillus subtilis. However, in B. subtilis it is believed that the system forms a stationary bipolar gradient from the cell poles to midcell. Here, we show that the Min system of B. subtilis localizes dynamically to active sites of division, often organized in clusters. We provide physical modelling using measured diffusion constants that describe the observed enrichment of the Min system at the septum. Modelling suggests that the observed localization pattern of Min proteins corresponds to a dynamic equilibrium state. Our data provide evidence for the importance of ongoing septation for the Min dynamics, consistent with a major role of the Min system to control active division sites, but not cell pole areas.

microbiology↗