Unique Role of Vimentin Networks in Compression Stiffening of Cells and Protection of Nuclei from Compressive Stress

In this work, we investigate whether stiffening in compression is a feature of single cells and whether the intracellular polymer networks that comprise the cytoskeleton (all of which stiffen with increasing shear strain) stiffen or soften when subjected to compressive strains. We find that individual cells, such as fibroblasts, stiffen at physiologically relevant compressive strains, but genetic ablation of vimentin diminishes this effect. Further, we show that unlike networks of purified F-actin or microtubules, which soften in compression, vimentin intermediate filament networks stiffen in both compression and extension, and we present a theoretical model to explain this response based on the flexibility of vimentin filaments and their surface charge, which resists volume changes of the network under compression. These results provide a new framework by which to understand the mechanical responses of cells and point to a central role of intermediate filaments in response to compression

Intraspecific Variation in Nectar Chemistry and Its Implications for Insect Visitors: The Case of the Medicinal Plant, Polemonium Caeruleum L.

Floral nectar, being a primary reward for insect visitors, is a key factor in shaping plant–pollinator interactions. However, little is known about the variability in nectar traits, which could potentially affect pollinators and the reproduction of the species. We investigated intraspecific variation in nectar traits in 14 populations of a Red-listed plant, Polemonium caeruleum. Populations varied in terms of the proportion of self-compatible and self-incompatible individuals, and insect communities visiting flowers. Using HPLC, we determined the nectar sugar and amino acid (AA) composition and concentration. We also recorded some basic habitat parameters, which could influence nectar chemistry. In seven selected populations, we investigated the taxonomic composition of the insects visiting flowers. Our observations revealed significant intraspecific variability in nectar chemistry in P. caeruleum. Nectar production was male-biased, with male-phase flowers secreting sucrose- and AA-rich nectar. An analysis revealed that variability in P. caeruleum nectar may be slightly shaped by environmental factors. The studied nectar characters, especially sugars, had little effect on insects visiting flowers. We argue that variation in nectar traits in this generalist plant is a matter of random genetic drift or “adaptive wandering” rather than directional specialization and adaptation in the most effective and abundant group of pollinators

Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents

Background: Infections caused by Candida spp. have become one of the major causes of morbidity and mortality in immunocompromised patients. Therefore, new effective fungicides are urgently needed, especially due to an escalating resistance crisis. Methods: A set of nanosystems with rod- (AuR), peanut- (AuP), and star-shaped (AuS) metal cores were synthesized. These gold nanoparticles were conjugated with ceragenins CSA-13, CSA-44, and CSA-131, and their activity was evaluated against Candida strains (n = 21) through the assessment of MICs (minimum inhibitory concentrations)/MFCs (minimum fungicidal concentrations). Moreover, in order to determine the potential for resistance development, serial passages of Candida cells with tested nanosystems were performed. The principal mechanism of action of Au NPs was evaluated via ROS (reactive oxygen species) generation assessment, plasma membrane permeabilization, and release of the protein content. Finally, to evaluate the potential toxicity of Au NPs, the measurement of hemoglobin release from red blood cells (RBCs) was carried out. Results: All of the tested nanosystems exerted a potent candidacidal activity, regardless of the species or susceptibility to other antifungal agents. Significantly, no resistance development after 25 passages of Candida cells with AuR@CSA-13, AuR@CSA-44, and AuR@CSA-131 nanosystems was observed. Moreover, the fungicidal mechanism of action of the investigated nanosystems involved the generation of ROS, damage of the fungal cell membrane, and leakage of intracellular contents. Notably, no significant RBCs hemolysis at candidacidal doses of tested nanosystems was detected. Conclusions: The results provide rationale for the development of gold nanoparticles of rod-, peanut-, and star-shaped conjugated with CSA-13, CSA-44, and CSA-131 as effective candidacidal agents

Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents

Background: Infections caused by Candida spp. have become one of the major causes of morbidity and mortality in immunocompromised patients. Therefore, new effective fungicides are urgently needed, especially due to an escalating resistance crisis. Methods: A set of nanosystems with rod- (AuR), peanut- (AuP), and star-shaped (AuS) metal cores were synthesized. These gold nanoparticles were conjugated with ceragenins CSA-13, CSA-44, and CSA-131, and their activity was evaluated against Candida strains (n = 21) through the assessment of MICs (minimum inhibitory concentrations)/MFCs (minimum fungicidal concentrations). Moreover, in order to determine the potential for resistance development, serial passages of Candida cells with tested nanosystems were performed. The principal mechanism of action of Au NPs was evaluated via ROS (reactive oxygen species) generation assessment, plasma membrane permeabilization, and release of the protein content. Finally, to evaluate the potential toxicity of Au NPs, the measurement of hemoglobin release from red blood cells (RBCs) was carried out. Results: All of the tested nanosystems exerted a potent candidacidal activity, regardless of the species or susceptibility to other antifungal agents. Significantly, no resistance development after 25 passages of Candida cells with AuR@CSA-13, AuR@CSA-44, and AuR@CSA-131 nanosystems was observed. Moreover, the fungicidal mechanism of action of the investigated nanosystems involved the generation of ROS, damage of the fungal cell membrane, and leakage of intracellular contents. Notably, no significant RBCs hemolysis at candidacidal doses of tested nanosystems was detected. Conclusions: The results provide rationale for the development of gold nanoparticles of rod-, peanut-, and star-shaped conjugated with CSA-13, CSA-44, and CSA-131 as effective candidacidal agents