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Segmented Fluorescence Correlation Spectroscopy (FCS) improves the accuracy of FCS measurements in cells by analyzing data in short temporal segments. We have recently demonstrated the possibility of performing segmented FCS using a commercial confocal laser scanning microscope, enabling the measurement of molecular diffusion in different subcellular regions. In this study, we apply segmented FCS to investigate the dynamics of poly(ADP-ribose) polymerase 1 (PARP1), a protein playing a central role in DNA damage response.

The mechanism behind osmolyte-induced protein stabilization remains elusive despite extensive research. Amongst various hypotheses, the associated water modulation hypothesis has proven to be the most effective in explaining osmolyte-induced stabilization effects. Earlier we had demonstrated that osmolytes that slow down associated water dynamics enhance protein thermal stability, whereas those that accelerate it, promote destabilization. However, the molecular basis of this correlation remains unclear.

Neural tissues of the central nervous system are among the softest and most fragile in the human body, protected from mechanical perturbation by the skull and the spine. In contrast, the enteric nervous system is embedded in a compliant, contractile tissue and subject to chronic, high-magnitude mechanical stress. Do neurons and glia of the enteric nervous system display specific mechanical properties to withstand these forces? Using nano-indentation combined with immunohistochemistry and second harmonic generation imaging of collagen, we discovered that enteric ganglia in adult mice are an order of magnitude more resistant to deformation than brain tissue.

The “holy grail” of chromatin research would be to follow the chromatin configuration in individual live cells over time. One way to achieve this goal would be to track the positions of multiple loci arranged along the chromatin polymer with fluorescent labels. Use of distinguishable labels would define each locus uniquely in a microscopic image but would restrict the number of loci that could be observed simultaneously, because of experimental limits to the number of distinguishable labels. Use of the same label for all loci circumvents this limitation but requires a (currently lacking) framework for how to establish each observed locus identity, i.e.

Fibrosis, marked by excessive extracellular matrix (ECM) accumulation, underlies functional decline in numerous diseases and often presents with sex-specific differences in severity. While biochemical pathways have been widely studied, the contribution of mechanical cues—particularly ECM stiffness—to these disparities remains unclear. Here, we develop an integrative mechanobiological model to investigate how estrogen modulates stiffness-mediated fibrotic progression. The model reveals that ECM stiffness activates fibroblasts through two key pathways: a rapid nuclear translocation of mechanosensitive factors (MRTF and TAZ) and a delayed TGF-β/Smad cascade, both of which enhance α-SMA expression and matrix production.

Atomic force microscope (AFM) indentation allows high-resolution spatial characterization of biomechanical properties of cells and tissues. Rapid, reproducible, and quantitative analysis of AFM force curves has been challenging due to several technical limitations, such as excessive noise and uncertainty associated with contact point determination. Here, we propose a novel machine learning (ML) algorithm, comprised of convolutional bidirectional long short-term memory neural networks called COBRA (Convolutional Bidirectional Recurrent Architecture) that can reliably process raw AFM elastography data, triage poor quality curves, and accurately identify the contact point without any a priori knowledge of underlying material properties.

Animal rhodopsin is a photoreceptive protein crucial for vision, with activation triggered by the cis–trans isomerization of a retinal chromophore upon light absorption. This activation involves a series of thermal intermediates, ultimately leading to G protein-mediated signal transduction. The retinal chromophore is covalently bound to the protein through a protonated Schiff base, and its deprotonation during the formation of the active intermediate is believed to induce structural changes in α-helices that facilitate G protein interactions.

Cell migration through constrictions is essential for many physiological processes. During this confined cell migration the protein nesprin-2, which links the cytoskeletal network to the nucleus, can accumulate at the front of the nucleus. Yet, up to now, the exact mechanism of this accumulation is unknown. Here, we further investigate this accumulation mechanism. We quantify the spatial distribution of nesprin-2, actin and the proteins SUN1 and SUN2, which are inner nuclear membrane proteins that bind to nesprin-2.

Epithelial-to-mesenchymal transition (EMT), a key process in cancer metastasis and fibrosis, disrupts cellular adhesion by replacing epithelial E-cadherin with mesenchymal N-cadherin. While, how the shift from E-cadherin to N-cadherin impacts molecular-scale adhesion mechanics and cluster dynamics—and how these changes weaken adhesion under varying mechanical and environmental conditions—remains poorly understood, limiting our ability to target EMT-driven pathological adhesion dynamics. Here, we developed a unified Lattice-Clutch model to investigate cadherin clustering, cortical tension, and adhesion strength during EMT.