- by Rembert, N., Dedenon, M., Roux, A., Dessalles, C. A.Cellular monolayers often exhibit orientational order, with nematic alignment of cell shape and cytoskeletal structures governing tissue-scale collective dynamics. Despite extensive studies, a unified analysis framework for characterizing active nematics in living systems remains partial, and key discrepancies with theory persist. Here, we present a systematic and comparative analysis of nematic order and tissue flow dynamics across twelve distinct cell types. We quantify the impact of analysis parameters and provide data-driven guidelines to improve reproducibility and cross-study comparability. Across all […]
- by Neumann, O. F., Kravikass, M., John, N., Ramachandran, R. G., Steinmann, P., Zaburdaev, V., Wehner, D., Budday, S.Functional spinal cord repair in zebrafish is governed by regeneration-favorable biochemical and mechanical cues within the lesion microenvironment. Alterations in extracellular matrix composition and stiffness are closely associated with axon regeneration. However, experimentally dissecting the interplay between mechanical signals and axonal regrowth in vivo remains technically challenging. Here, we present an agent-based modeling framework to simulate stiffness-mediated axonal growth trajectories across the lesion. We use this model to explore potential mechanisms underlying the characteristic growth patterns observed during zebrafish spinal […]
- by Fuertes, C., Gonzalez, J. E., Suesca, E., Guzman-Sastoque, P., Munoz, C., Manrique-Moreno, M., Carazzone, C., Leidy, C.Staphylococcus aureus (S. aureus) is an opportunistic pathogen that is a global health concern for its ability to cause a wide spectrum of clinical infections. Due to the emergence of resistance to commonly used antibiotics, there has been interest in exploring the use of antimicrobial peptides to treat S. aureus infections. However, changes in the lipid composition of the lipid bilayer membrane can alter the activity of peptides, and S. aureus is able to induce variations in lipid composition in […]
- by Hekstra, D. R., Wang, H. K., Choe, A. K.Perturbative X-ray crystallography can visualize functional dynamics and conformational changes in proteins at atomic resolution. During a typical perturbative crystallography experiment, only a fraction of protein molecules in a crystal will be perturbed, or "excited". As a result, the observed data represent a mixture of excited and ground states. The conventional approach to estimating the excited-state structure factor amplitudes is to linearly extrapolate the difference between the structure factor amplitudes of the perturbed and unperturbed data. This approach often fails […]
- by America, P., Ostrofet, E., Johnson, B., Quack, S., Papini, F., Smitskamp, Q., Buc, D., Arnold, J. J., Cameron, C. E., Dulin, D.High-throughput force spectroscopy assays, such as with magnetic tweezers, enable reconstruction of biomolecular reaction energy landscapes and provide access to rare events with deep statistics. Precise force calibration is essential for accurately describing complex reactions, which can be hindered by sample heterogeneity, such as bead-to-bead difference in magnetic content. Here, we describe an in-situ force calibration methodology for high-throughput magnetic tweezers that enables the calibration for each individual bead with an accuracy of up to 3%, limited only by the […]
- by Ghosh, S., Das, C. K., Naskar, S., Schäfer, L. V., Happe, T.[FeFe]-hydrogenases are metalloenzymes that catalyze the reversible oxidation and production of H2, making them potential candidates for sustainable energy solutions. However, their practical application is restricted by their extreme O2 sensitivity, which leads to irreversible active site degradation. A newly characterized Group B hydrogenase, ToHydA from Thermosediminibacter oceani, has exhibited exceptional O2-stability even after longtime exposure to air. In ToHydA, the highly conserved proton-transporting cysteine (C212) safeguards the H-cluster from O2-induced degradation by formation of the Hinact state. In this […]
- by AZOTE epse HASSIKPEZI, S., Negi, R. S., Chen, N., Manning, M. L.Stratified epithelial tissues such as the skin epidermis maintain barrier integrity during development and homeostasis through the coordinated action of cell proliferation, differentiation, delamination, and tissue-scale mechanical forces. During development, the orientation of cell division within the basal layer plays a pivotal role in tissue stratification; however, the mechanical principles linking the orientation of the division plane to these processes across developmental stages remain poorly understood. Here, we expand a recently developed three-dimensional vertex model for stratified epithelia, composed of […]
- by Lubart, Q., Levin, S., de Carvalho, V., Persson, E., Block, S., Joemetsa, S., Olsen, E., KK, S., Gorgens, A., EL Andaloussi, S., Hook, F., Bally, M., Westerlund, F., Esbjorner, E. K.Extracellular vesicles (EVs) are cell-secreted biological nanoparticles that play a crucial role in intercellular communication and are gaining increasing attention as diagnostic biomarkers, therapeutic agents, and drug delivery vehicles. Consequently, the development of robust and sensitive methods for their characterization is essential. Herein we present the use of a microscope-mounted nanofluidic device for direct size determination and multi-parametric (3-color) fluorescence-based phenotyping of single biological nanoparticles that are in the size range of 20-200 nm in a method we denote Nano-SMF […]
- by Tsutsumi, M., Saito, N., Yamaguchi, T., Sasaki, T., Furusawa, C.Accurate shell shape quantification is critical for studying biodiversity and evolution, yet intraspecific variability in bivalves makes morphology-based identification difficult. Traditional methods, including landmark-based analyses and elliptic Fourier descriptors, suffer either from subjectivity in homologous point selection or from limited use of contour information. Here, we introduce Morpho-VAE, a deep generative framework integrating a variational autoencoder with a supervised classifier, to analyze shell images of five textit{Anadara} species. Morpho-VAE outperforms conventional approaches in species classification by embedding morphological variation into […]
- by Uckermann, O., Leonidou, T., Rix, J., Temme, A., Eyüpoglu, I. Y., Galli, R.Objective and Rationale: Brain biomechanics is a rapidly evolving field, with mechanical properties influencing both normal development and pathological conditions such as cancer. Brillouin microscopy, a non-contact optical technique, offers a promising approach for studying the biomechanics of fresh brain tumors and organoids at subcellular resolution. However, challenges such as tissue heterogeneity and signal attenuation necessitate an in-depth evaluation of measurement strategies and potential confounding factors. Methods: Fresh human brain tumor samples and tumor organoids were analyzed using Brillouin microscopy […]
- by Benchimol-Barbosa, P. R., Loayza-Benchimol-Barbosa, A. C., Carvalhaes, C. G., Kantharia, B. K.AbstractO_ST_ABSBackgroundC_ST_ABSLeft ventricular (LV) remodeling in chronic Chagas cardiomyopathy (CCC) is progressive, but whether population-level LV mass dynamics follow nonlinear patterns and whether the loss of dynamic complexity tracks mortality is unknown. MethodsFifty outpatients from SEARCH-Rio cohort were followed-up for 10 years. Serial echocardiography provided paired LV mass measurements fitted to the logistic equation x = {middle dot}x{middle dot}(1-{gamma}{middle dot}x). Lyapunov exponents (LE) were computed from consecutive inter-patient derivatives. A clinical risk score was developed using Firth penalized logistic regression with […]
- by Anantha Krishnan, A., Dinning, P. G., Holland, M. A.PurposeColonic motility disorders, including diarrhea-predominant irritable bowel syndrome and slow-transit constipation, impose a major clinical burden. Although high-resolution colonic manometry reveals characteristic spatiotemporal motor patterns, such as high-amplitude propagating contractions and cyclic motor pattern in healthy individuals, these patterns are often altered or absent in disease. Understanding how these patterns arise from underlying pacemaker, neural, and mechanical mechanisms is essential for improving treatment strategies. MethodsWe developed a biophysical whole-colon model that integrates an Interstitial Cells of Cajal-inspired oscillator network, enteric […]
- by Plum, A. M., Serra, M.During development, embryos store, transmit, and transform information to generate spatial patterns. Positional information (PI) quantifies how precisely cells form patterns at a given time, but cell motion has limited its application to static tissues. We introduce a framework for PI in dynamic tissues by decomposing mutual information between cells' positions and properties over time into information flows contributing to PI preservation, loss and generation. These reveal information-theoretic signatures of ubiquitous developmental processes, including instruction, sorting and mixing, directly from […]
- Small-Molecule Structure Determination and Anisotropic Displacement Analysis at Turkish Light Sourceby AYAN, E., Mermer, A.Single-crystal X-ray diffraction remains one of the most direct and reliable techniques for clarifying the three-dimensional structures of small molecules; however, its wider use in developing research settings has historically been limited by access to advanced instrumentation. Here, we consider the performance of the in-house diffractometer, Turkish Light Source, for small-molecule structure determination using three rhodanine-derivative compounds. Diffraction data were collected, processed, and followed by full-matrix least-squares refinement as a user-friendly pipeline. The compounds were successfully resolved in the triclinic […]
- by Li, D., Yang, S., Xiao, Q., Niu, T., Zhang, Y., Zhu, Y., Sun, F.Cryo-electron microscopy (cryo-EM) is the mainstream method for structure determination, yet current automated workflows remain rigid and require expert intervention for failure recovery, heterogeneity analysis, and optimization. We present cryoAgent, an agentic workflow for autonomous cryo-EM image processing with adaptive tool use to address these challenges. cryoAgent improves reconstruction quality across diverse datasets, identifies a previously unreported structural state, and outperforms state-of-the-art automated workflows, advancing scalable and discovery-oriented structural biology.
- by Dolorfino, M. D., Santos Perez, D., Fu, Y., Lin, S.-H., McCarty, S., O'Meara, M. J., Sztain, T.DNA-encoded libraries (DELs) enable ultra-large screening of billions of molecules simultaneously. However, various limitations of DELs have prompted interest in training machine learning (ML) models on these large datasets to extrapolate predictions to non-DEL compounds. A recent NeurIPS competition revealed that even top performing ML models trained on DEL data failed at generalizing to out-of-distribution (OOD) chemical space. We investigated whether integrating structural modeling could bridge this generalization gap. We systematically assessed state-of-the-art ML, docking, and co-folding methods with three […]
- by Killeen, T. D., Stoneman, M., Popa, I., Chen, Q., Raicu, V.Investigations of G protein-coupled receptors (GPCRs) interactions with non-visual arrestins in living cells are essential to understanding the complex molecular mechanisms of GPCR-based signaling. Quantitative analysis of these interactions remains challenging in live cells, particularly when attempting to repeatedly image distinct cellular regions with high precision. Here, we describe the implementation of an optical imaging stabilization approach that integrates the recently developed Focal Readjustment for Enhanced Vertical Resolution (FREVR) technology into a multiphoton microscope, enabling high-precision alternation between image-forming sample […]
- by Ghosh, K., Gupta, M., Voth, G. A.One of the key events in the HIV-1 life cycle is reverse transcription, during which single-stranded viral RNA (ssRNA) is converted into double-stranded DNA (dsDNA). This process occurs inside the mature virus capsid and, once it reaches a critical threshold, drives capsid rupture. This uncoating is essential for infection because it releases viral genetic material into the host cell nucleus. Despite its importance, many mechanistic details of this process remain poorly understood. To address this gap, we develop a multiscale […]
- by Chu, A. L., Chu, B. S. L., Qiang, W.Formation of the {beta}-amyloid (A{beta}) plaques is a pathological hallmark of Alzheimers disease (AD), and is believed to be a primary cause of dementia in elderly individuals. In the present work, we simulated the conformational evolution of A{beta}42 dimers in solution and in membrane-like environment to explore the folding of A{beta}42 along fibrillation. The molecular dynamics (MD) simulation was steered by experimental internuclear distance restraints obtained using solid-state nuclear magnetic resonance (ssNMR) spectroscopy. Our results revealed that several hydrophobic and […]
- by Haspel, N., Jang, H., Nussinov, R.Rac2, a member of the Rho family of small GTPases, is a fundamental regulator of essential cellular processes. Pathogenic substitutions near and within the Switch II region, specifically D57N and E62K, have been implicated in oncogenesis and immunodeficiency. Despite their proximity, D57N is characterized as a loss-of-function mutation, while E62K is a constitutively active, gain-of-function mutation. In this study, we addressed several critical questions: (i) the structural basis of their altered cellular functions, (ii) how these variants rearrange the conformational […]
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