Actin filaments are essential components of the cytoskeleton. Their structural polarity, characterized by distinct 'plus' (barbed) and 'minus' (pointed) ends, is crucial for the directional growth and dynamic behavior of actin filaments during cellular processes such as motility, division, and intracellular transport. Asymmetric and directional filament formation is highly regulated by the bound nucleotide

Potassium ion channels are responsible for the rapid selective conduction of K + ions through the cellular membrane. In 1955, Hodgkin and Keynes showed that K + channel conduction occurs via a multi-ion process in which 2-3 ions diffuse in single file along a narrow pore. This process is now commonly referred to as the "knock-on" mechanism. The availability of the crystallographic structure of the

Synapsins are the proteins responsible for recruiting synaptic vesicles into the synaptic vesicle cluster. As one of the most abundant synaptic proteins, synapsins are well known to directly interact with the synaptic vesicles, but they can also interact with planar membranes, notably the synaptic membrane, at least indirectly by tethering vesicles to the active zone. In order to contribute to a quantitative

Membrane fusion is central to biological processes such as viral entry, fertilization and cell-to-cell fusion. Gaining a mechanistic understanding of fusion requires the ability to visualize and quantify the dynamic interaction between two membranes and their associated protein machineries at high temporal and spatial resolution. However, studying these processes in live cells remains challenging due

Biomolecular condensates are membraneless intracellular structures formed from the phase separation of proteins and nucleic acids. Although biomolecular condensates do not have a phospholipid membrane at their surface, recent studies reveal conspicuous assemblies of proteins at the interface between the dense and dilute phases of nucleoli, P granules, and other condensates. The molecular and biophysical

The main thermodynamic force opposing protein folding is the loss of the polypeptide conformational entropy. Backbone conformational entropy, as well as other thermodynamic forces associated with folding, are difficult to measure directly, even for simple model systems such as α-helices. Helix-coil theories describe α-helix folding as a process involving the loss of backbone conformational freedom

Cells in load-bearing tissues experience both solid deformation and interstitial fluid flow during physiological loading, but the mechanisms by which they integrate these poroelastic mechanical signals remain poorly understood. Here, we develop a porous, nanoarchitected 3D scaffold that allows simultaneous delivery and control of matrix strain and fluid shear stress. We validated the platform through

Chromatin organization is essential for DNA packaging and gene regulation in eukaryotic genomes. While significant progresses have been made, the exact molecular arrangement of nucleosomes remains controversial. Using a well-calibrated residue-level coarse-grained model and advanced dynamics modeling techniques, particularly the non-Markovian dynamics model, we map the free energy landscape of tetra-nucleosome

We report that axons of cortical neurons, structurally intricate excitable media, maintain remarkably high fidelity in transmitting somatic spike timing, even during complex spontaneous network activity that includes extremely short (2–3 msec) inter-spike intervals. This robustness underscores their function as reliable conducting devices under physiological conditions. It is nevertheless well established

The protein hydration shell is a key mediator of processes such as molecular recognition, protein folding, and proton transfer. How surface-exposed amino acids shape the hydration shell structure is not well understood. We combine molecular dynamics simulations with explicit-solvent predictions of small-angle X-ray scattering (SAXS) curves to quantify the contributions of all 20 proteinogenic amino

Magnetotactic bacteria (MTB) utilize magnetosomes to navigate along magnetic fields and employ photosensitive proteins to respond to light. However, whether a synergistic mechanism exists between phototaxis and magnetotaxis remains unclear. To investigate the cooperative roles of the magnetosensitive protein Amb0994 and the photosensitive protein Amb2291 under magnetic reversal and coupled magneto-optical

Organisms frequently encounter abiotic stresses such as drought, salinity, and extreme temperatures, requiring sophisticated adaptive mechanisms. Stress memory enables them to respond more efficiently to repeated environmental challenges by retaining information from prior exposures. Biomolecular condensates, dynamic, membrane-less cellular assemblies formed by liquid-liquid phase separation, have

Cold atmospheric plasma (CAP) generates various products, including radiation, electrons, ions, electric field (EF) and reactive oxygen and nitrogen species. CAP promotes wound healing and has been implemented as several medical devices to treat acute or chronic wounds. Beyond the closure of the epidermal monolayer of keratinocytes, wound healing requires migration of dermal fibroblasts. The effect

Tau is a microtubule-associated protein that plays a critical role in regulating the organization and stability of microtubules (MTs) in neurons. Although the association of tau with MTs is well recognized, the structural consequences of its binding at steady state have remained poorly understood. Here, we combined small-angle x-ray scattering with AlphaFold predictions and high-resolution modeling

Macromolecules, such as proteins, antibodies, nanobodies, and other affinity binders, play essential roles in therapeutic and diagnostic applications due to their high specificity and functionality. Understanding their structure is critical for deciphering their biological activity and drug discovery; however, the inherent complexity of these molecules poses significant challenges. Computational approaches

Epithelial-mesenchymal plasticity is a cell-fate switching program that enables cells to adopt a spectrum of phenotypes ranging from epithelial (E) to mesenchymal (M), including intermediate hybrid E/M states. Hybrid E/M phenotypes are conducive to cancer metastasis, as they are associated with metastatic initiation, cancer stemness, drug resistance, and collective migration. Boolean models of the

Liquid-liquid phase separation (LLPS) is one mechanism that cells can use to organize biomolecules spatially and functionally. Some coiled-coil (CC) proteins, such as the centrosomal proteins pericentrin and spd-5, are thought to undergo LLPS, but it is currently unknown what parts of these proteins facilitate the process. It is thought, however, that the numerous CC domains in these proteins might

The conformational variability of RNA duplexes with internal loop 5′GAGU/3′UGAG was investigated by nuclear magnetic resonance (NMR) spectroscopy and all-atom molecular dynamics (MD) simulations. It was previously found that the CG-flanked internal loop in 5′GACGAGUGUCA/3′ACUGUGAGCAG existed in a major conformation (I) characterized by U7 and U7∗ bulging into solution, A5 and A5∗ stacking, and G4-G6∗

The intercalated disk (ID) is a structurally heterogeneous junctional complex essential for synchronized cardiac conduction and contraction. Previous computational models have investigated the influence of ID structure on cardiac conduction. However, most have relied on oversimplified geometries and uniformly distributed ion channels, limiting their ability to capture nanoscale heterogeneity. In this

When we hear, sound-induced deflections of our sensory outer-hair-cell bundles are transduced into receptor currents. These receptor currents drive the cochlear amplifier, which is required for our ear’s high sensitivity, broad dynamic range, and sharp frequency selectivity. Adaptation maintains the sensitivity of receptor currents to bundle deflections, but the mechanisms underlying adaptation in

The precise positioning and orientation of mitotic spindles are critical for ensuring accurate segregation of daughter cells during tissue development. Spindle positioning machinery—composed of astral microtubules and motor proteins—must withstand diverse mechanical forces, requiring robust mechanical properties. However, due to the difficulty in experimental measurements, the viscoelastic properties

Bacteriocins are ribosomally synthesized antimicrobial peptides that often rely on specific membrane receptors for activity. Among these receptors, the mannose-specific phosphotransferase system (Man-PTS) is a conserved bacterial target for structurally diverse peptides. While most Man-PTS-binding bacteriocins share a canonical β-sheet/α-helix fold, members of the GarC-like subgroup exhibit an atypical

Cell and extracellular matrix interactions are essential for maintaining tissue function and homeostasis. Changes in the biochemical or mechanical properties of the extracellular matrix can lead to diseases such as fibrosis or cancer. In a 3D microenvironment, cell-matrix interaction is vital to how cells sense and respond to biochemical and biophysical cues. This study examines the reciprocal interactions

Fibrinogen plays a central role in the physiological processes of blood coagulation and, unfortunately, ischemic stroke, where it is routinely exposed to mechanical forces. In this study, we employed atomistic molecular dynamics simulations to subject fibrinogen to three cycles of high-strain loading (∼17.5–27.5%) and unloading, enabling us to probe its mechanical response under cyclic stress. To capture

A living cell is a nonequilibrium thermodynamic system where, nevertheless, a notion of local equilibrium exists. This notion applies to all micro- and nanoscale aqueous volumes, each containing a large number of molecules. This allows one to define sets of local conditions, including thermodynamic ones; for instance, a defined temperature requires thermodynamic equilibrium by definition. Once such

Supramolecular assemblies that can spontaneously disassemble in response to specific protein binding provide a powerful platform for sensing and targeted delivery. This concept has been previously demonstrated using a peptide-based amphiphilic polymer (P1) that consists of both hydrophobic M1 and hydrophilic M2 and M3 side chains and presents a specific ligand for protein bovine carbonic anhydrase

Two phylogenetically distinct groups of microbial rhodopsins show light-induced inward proton transport activity, xenorhodopsins (XeRs) and schizorhodopsins (SzRs). However, structural insights into inward proton pumps are limited, as only three structures have been determined to date, Nanosalina xenorhodopsin (NsXeR), Bacillus coahuilensis xenorhodopsin (BcXeR), and Lokiarchaeota archaeon Schizorhodopsin-4

Accurate measurements of cellular forces are important for understanding a wide range of biological processes where traction plays a major role. The characterization of mechanical properties is needed to unravel complex phenomena like migration, morphogenesis, mechanotransduction, or shape regulation, but accurate data on large numbers of single cells remain scarce and challenging. The capacity to

The bacterial cytoplasm is characterized by a distinctive membrane-less organelle, the nucleoid, which harbors the chromosomal DNA. We investigate the steric effects of dynamic processes associated with transcription and translation on the structure of this organelle using coarse-grained molecular dynamics simulations that incorporate out-of-equilibrium reactions. Our model captures the scale of the

Cell staining techniques are essential for cell visualization and bioanalysis, providing valuable insights into cellular structure, function, and behavior. Despite their significance, the impact of staining processes, such as dye penetration, adsorption, or hydrogen bonding, on the physical properties of cells remains largely unexplored. Acoustic methods have proven effective in noninvasively probing

Small-angle x-ray scattering (SAXS) has evolved over the past decades into an essential structural biology technique for the study of conformational states of solubilized biomacromolecules and assemblies. It complements a multitude of other methods, including the atomic-resolution techniques NMR, crystallography, and cryo-EM. In the vast majority of applications, the biological systems of interest

Melanopsin, a G-protein coupled receptor (GPCR) and photopigment, mediates nonimage-forming and image-forming visual behaviors. There are six subtypes of intrinsically photosensitive retinal ganglion cells (ipRGCs) in the mouse retina; although melanopsin signals through Gαq in all subtypes, evidence suggests that M1 and M4 ipRGCs may utilize distinct phototransduction pathways. We sought to uncover

A high degree of structural complexity arises in dynamic neuronal dendrites due to extensive branching patterns and diverse spine morphologies, which enable the nervous system to adjust function, construct complex input pathways, and thereby enhance the computational power of the system. Recognition of pathological changes due to neurodegenerative disorders is of crucial importance due to the determinant

Sorting nexins (SNXs) are a large group of diverse cellular trafficking proteins that play essential roles in membrane remodeling and cargo sorting between organelles. SNX proteins comprise a banana-shaped BAR domain that acts as a curvature-inducing scaffold and a phosphoinositide lipid-sensitive phox homology domain (PXD) that interacts with the membrane to ensure specific and efficient organelle

The Aβ42 peptide (APP(672–713)), associated with Alzheimer disease, is highly prone to form amyloid fibrils and has been extensively studied through in vitro experiments. Such experiments represent a basis for understanding the biophysical chemistry of amyloid-related diseases. In this communication, we show that homogeneous primary nucleation in vitro of Aβ42 fibrils is a very rare event, implying

Protein complexes perform biological functions through specific structural assemblies. Although experimental techniques and AI-driven methods have resolved structures of numerous protein complexes, their assembly orders of subunits remain largely unknown. Understanding the assembly order of a protein complex is crucial for in vitro drug synthesis, subcomplex engineering, and elucidating biological

The nascent polypeptide exit tunnel (NPET) is a subcompartment of the ribosome that constrains the dynamics of nascent polypeptide chains during protein translation. Simulating these dynamics has been limited by the spatial scale of the ribosome and the temporal scale of elongation. Here, we present an automated pipeline to extract the geometry of the NPET and the ribosome surface at high resolution

The acto-myosin cytoskeleton is a key driver of cellular shape changes in vivo and in vitro. Acto-myosin organization results from actin assembly and interactions between actin and myosin, which are both regulated by small Rho GTPases like Rac1 and RhoA. To uncover principles governing cytoskeletal organization, we analyzed actin patterns using live microscopy and theory in flat cortical layers of

G-protein-coupled receptors are key drug targets due to their role in cellular signaling. Among them, bistable rhodopsins such as the jumping spider rhodopsin 1 (JSR1), are promising for optogenetic applications, but their transduction mechanisms remain poorly understood. In this study, we used microsecond equilibrium molecular dynamics simulations, network analysis, and machine learning to investigate

Leukocyte deformability is important for the function of these cells as they undergo passage through the vasculature and adhere and deform on the endothelium, particularly in the microvasculature. Existing mechanical descriptions of the cell fail to account completely for cell behavior, even when cells are in the passive state. We present new evidence of a persistent elastic contribution to the stresses

Lysine residues in proteins are frequently modified posttranslationally, adding functional complexity to the proteome and playing critical roles in cellular regulation and disease. However, modeling these modifications in 3D protein structures remains challenging due to the limited availability of accessible and high-throughput computational tools. We present ptmK, a lightweight, standalone toolkit

Peripheral somatosensory neurons in the dorsal root ganglia (DRG) transduce mechanical force in the skin and other organs into electrical signals using specialized mechanically activated (MA) ion channels that initiate neuronal activation in response to force. Increasing evidence highlights PIEZO2 as the primary transducer of low-threshold mechanical force in DRG neurons. However, in the absence of

Touch sensation starts with the opening of mechanically gated activated ion channels at neuroglial endings of mechanoreceptors in the skin. The function of around half of low-threshold mechanoreceptors is dependent on the presence of the mechanically gated ion channel PIEZO2. It has been reported that particularly rapidly adapting mechanosensitive currents (RA currents) in the cell bodies of acutely

The basic helix-loop-helix Per-Arnt-Sim (bHLH-PAS) transcription factors (TFs) are regulators of several critical cellular functions such as circadian rhythm, hypoxia response, and neuronal development. Although PAS domains adopt a conserved fold, recent studies suggest that their interaction interfaces differ distinctly in different TF complexes. However, the implications of these differences on the

Atomic force microscopy (AFM) is widely used to measure the elastic properties of living cells, typically by extracting the Young’s (elastic) modulus from force-indentation curves acquired at a fixed loading rate. However, it is increasingly clear that cells relax applied stresses over time and exhibit significant frequency-dependent loss properties, a phenomenon that figures centrally in many biological

Neuronal acidic protein of 22 kDa (NAP-22, also called CAP23 or BASP1) is a myristoylated protein highly expressed in brain (> 0.4% of the total protein), and it highly localizes in the presynaptic region. NAP-22 was found to be a major component of detergent-resistant membrane fraction of brain, indicating its affinity to the cholesterol-enriched lipid domains (lipid rafts). In addition to several

Integral membrane proteins such as G-protein-coupled receptors (GPCRs), including visual pigments, are critical targets in both fundamental and pharmaceutical research. However, low expression levels and intrinsic instability often hinder their functional and structural characterization. Therefore, efficient screening methods are needed to identify suitable candidates for biochemical and biophysical