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Milovanovic, D.

Publications and source records attributed to Milovanovic, D..

21 records · Page 2Linked to original sources

More than just oil droplets in water: surface tension and viscosity of protein condensates quantified by micropipette aspiration

The material properties of biomolecular condensates play pivotal roles in many biological and pathological processes. Despite the rapid increase in the number of biomolecules identified that undergo liquid-liquid phase separation (LLPS), quantitative studies of the resulting condensates have been severely lagging behind. Here, we develop a micropipette-based technique, which uniquely allows quantifications of both the surface tension and viscosity of biomolecular condensates, independent of labeling and surface wetting effects. We demonstrate the accuracy and versatility of this technique by measuring condensates of LAF-1 RGG domains and a polymer-based aqueous two-phase system (ATPS). We anticipate this technique will be widely applicable to biomolecular condensates and will resolve several limitations regarding current approaches.

biophysics↗

SARS-CoV-2 infection induces mixed M1/M2 phenotype in circulating monocytes and alterations in both dendritic cell and monocyte subsets

Clinical manifestations of SARS-CoV-2 infection range from mild to critically severe. The aim of the study was to highlight the immunological events associated with the severity of SARS-CoV-2 infection, with an emphasis on cells of innate immunity. Thirty COVID-19 patients with mild/moderate symptoms and 27 patients with severe/critically severe symptoms were recruited from the Clinical Center of Kragujevac during April 2020. Flow cytometric analysis was performed to reveal phenotypic and functional alterations of peripheral blood cells and to correlate them with the severity of the disease. In severe cases, the number of T and B lymphocytes, dendritic cells, NK cells, and HLA-DR-expressing cells was drastically decreased. In the monocyte population proportion between certain subsets was disturbed and cells coexpressing markers of M1 and M2 monocytes were found in intermediate and non-classical subsets. In mild cases decline in lymphocyte number was less pronounced and innate immunity was preserved as indicated by an increased number of myeloid and activated dendritic cells, NK cells that expressed activation marker at the same level as in control and by low expression of M2 marker in monocyte population. In patients with severe disease, both innate and adoptive immunity are devastated, while in patients with mild symptoms decline in lymphocyte number is lesser, and the innate immunity is preserved.

immunology↗

Cell surface mechanics gate stem cell differentiation

Cell differentiation typically occurs with concomitant shape transitions to enable specialized functions. To adopt a different shape, cells need to change the mechanical properties of their surface. However, whether conversely cell surface mechanics control the process of differentiation has been relatively unexplored. Here, we show that membrane mechanics gate the exit from naive pluripotency of mouse embryonic stem cells. By measuring membrane tension during differentiation, we find that naive stem cells release their plasma membrane from the underlying actin cortex when transitioning to a primed state. By mechanically tethering the plasma membrane to the cortex with a synthetic signalling-inert linker, we demonstrate that preventing this detachment forces stem cells to retain their naive pluripotent state. We thus identify a decrease in membrane-to-cortex attachment as a new cell-intrinsic mechanism that is essential for stem cells to exit pluripotency.

biophysics↗