Biology subjects

Rädler, J. O.

Publications and source records attributed to Rädler, J. O..

3 recordsLinked to original sources

bioRxiv2025

Conserved and Lineage-Specific Roles of KEA-Mediated Ion Homeostasis in Chlamydomonas

In Arabidopsis thaliana, seamless plastid gene expression and development depend on finely balanced ion homeostasis across the inner envelope (IE) membrane, maintained by the K/H antiporters AtKEA1/2. To assess whether these functions are retained across mono- and polyplastidic representatives of the green lineage, we studied CrKEA1, the sole IE KEA homolog in the unicellular alga Chlamydomonas reinhardtii. Using CRISPR/Cas9, we generated a Cr-kea1 knockout mutant that exhibits impaired photoautotrophic growth, chloroplast deformation, and photoinhibition. Transcriptomics revealed strong induction of ribosome biogenesis genes and reduced abundance of transcripts associated with cell and plastid division. Further RNA analyses confirmed defects in stromal rRNA maturation of Cr-kea1, paralleling observations from Arabidopsis kea1kea2 mutants. Expression of CrKEA1 in Arabidopsis rescued growth and rRNA maturation in At-kea1kea2, demonstrating functional continuity after the ancient divergence between the two lineages. Cross-species transcriptomic comparisons further revealed that IE KEA loss elicits both shared and species-specific transcriptional responses: PhANG repression was conserved between algae and plants, whereas activation of the chloroplast unfolded protein response (cpUPR) and reduced expression of genes tied to cell-cycle and plastid fission occurred only in Chlamydomonas. Single-cell time-lapse imaging confirmed that Cr-kea1 exhibits an increased frequency of aberrant cytokinesis, unequal division, and division failure. Our findings demonstrate that while IE KEA transporters fulfill conserved roles in maintaining the conditions for plastid gene expression, their integration into broader cellular networks has diverged between unicellular chlorophytes and embryophytes (land plants). This underscores a lineage-dependent tuning of plastid-nucleus communication shaped by organismal complexity and plastid number. One-sentence summaryDisruption of KEA-mediated chloroplast ion homeostasis in Chlamydomonas reinhardtii reveals conserved and lineage-specific control of plastid rRNA processing and cell cycle progression.

plant biology↗

bioRxiv2025

Buffer specificity of ionizable lipid nanoparticle transfection efficiency and bulk phase transition

Lipid nanoparticles (LNPs) are efficient and safe carriers for mRNA vaccines based on advanced ionizable lipids. It is understood that the pH dependent structural transition of the mesoscopic LNP core phase plays a key role in mRNA transfer. However, buffer specific variations in transfection efficiency remain obscure. Here we analyze the effect of buffer type on the structure and transfection efficiency of LNPs. We find that LNPs formulated with the cationic ionizable lipid DLin-MC3-DMA (MC3) in citrate compared to phosphate and acetate buffers exhibit earlier onset and stronger mRNA-GFP expression in-vitro. Using synchrotron small angle X-ray scattering (SAXS) we determine the pH dependent mesophases of ionizable lipid MC3/cholesterol/water dialyzed against the various buffers. The results show that the phase transition with decreasing pH from inverse micellar cubic to inverse hexagonal (Fd3m-HII) is shifted by one unit to a lower transition pH for acetate and phosphate compared to citrate buffer. Based on continuum theory and ion specific adsorption obtained from all-atom MD simulations, we propose a mechanism for buffer specificity. Citrate stabilizes the inverse hexagonal phase thus shifting the formation of HII to a higher pH. By contrast, phosphate and acetate stabilize LII. We propose that the Fd3m-to-HII transition, which is facilitated in citrate buffer, is responsible for a sensitized pH-response of the LNP core phase. This, in turn, enhances endosomal release efficiency and accounts for the earlier onset of gene expression observed in LNPs prepared with citrate buffer.

biophysics↗

bioRxiv2022

On multistability and constitutive relations of cell motion on Fibronectin lanes

Cell motility on flat substrates exhibits multistability between steady and oscillatory morphodynamics, spread and moving states, the biphasic adhesion-velocity relation, and the universal correlation between speed and persistence (UCSP) as simultaneously observed phenomena. Their universality and concurrency suggest a unifying mechanism to exist causing all of them. We search for that mechanism by investigating trajectories of MDA-MB-231 cells on Fibronectin lanes. We also find multistability caused by the clutch mechanism of retrograde flow. Control of the clutch parameters by integrin signalling causes the biphasic adhesion-velocity relation. Protrusion competition based on the clutch causes direction reversal events, the statistics of which explains the UCSP. We suggest that F-actin polymerisation, clutch mechanism of retrograde flow, protrusion competition via membrane tension and drag forces cause the multistability and dynamic cell states, state transition statistics causes the UCSP and the control of this dynamic system by integrin signalling entails the adhesion-velocity relation.

biophysics↗