Biology subjects

Lerche, M. H.

Publications and source records attributed to Lerche, M. H..

2 recordsLinked to original sources

bioRxiv2022

Quantitative Evaluation of the Cellular Uptake of Nanodiamonds by Monocytes and Macrophages

Nanodiamonds (NDs) with NV- defect centers are great probes for bionanotechnology applications, with potential to act as biomarkers for cell differentiation. To explore this concept, uptake of NDs (~120nm) by THP-1 monocytes and monocyte-derived M0-macrophages is studied. The time course analysis of ND uptake by monocytes confirms differing ND-cell interactions and a positive time-dependence. No effect on cell viability, proliferation and differentiation potential into macrophages is observed, while cells saturated with NDs, unload the NDs completely by 25 cell divisions and subsequently take up a second dose effectively. ND uptake variations by THP-1 cells at early exposure-times indicate differing phagocytic capability. The cell fraction that exhibits relatively enhanced ND uptake is associated to a macrophage phenotype which derives from spontaneous monocyte differentiation. In accordance, chemical-differentiation of the THP-1 cells into M0-macrophages triggers increased and homogeneous ND uptake, depleting the fraction of cells that were non-responsive to NDs. These observations verify that ND uptake allows for distinction between the two cell subtypes based on phagocytic capacity. Overall, NDs demonstrate effective cell labeling of monocytes and macrophages, and are promising candidates for tracking biological processes that involve cell differentiation.

cell biology↗

bioRxiv2019

Mutations in a single signaling pathway allow growth on a different solvent than water

Since life is completely dependent on water, it is difficult to gauge the impact of solvent change. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D2O), and investigated the biological effects by a wide range of techniques, using the fission yeast Schizosaccharomyces pombe as model organism. We show that high concentrations of D2O lead to altered glucose metabolism, growth retardation, and inhibition of meiosis. However, mitosis and overall cell viability were only slightly affected. After prolonged incubation in D2O, cells displayed gross morphological changes, thickened cell walls as well as aberrant septa and cytoskeletal organization. RNA sequencing revealed that D2O causes a strong downregulation of most tRNAs and triggers activation of the general stress response pathway. Genetic screens identified several D2O sensitive mutants, while mutants compromised in the cell integrity pathway, including the protein kinase genes pmk1, mkh1, pek1 and pck2, that control cell wall biogenesis, were more tolerant to D2O. We speculate that D2O affects the phospholipid membrane or cell wall glycans causing an activation of the cell integrity pathway. In conclusion, the effects of solvent replacement are pleiotropic but the D2O-triggered activation of the cell integrity pathway and subsequent increased deposition of cell wall material and septation problems appear most critical for the cell growth defects.

genetics↗