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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 remained poorly understood. Here, we combined small-angle X-ray scattering (SAXS) with AlphaFold predictions, and high-resolution modeling using our D+ software, to investigate how tau modulates the MT architecture in-vitro. We reconstituted a minimal model system of dynamic MTs with purified tubulin and then added either full-length tau (FL-tau, or 2N4R) or a minimal 4-repeats tau construct (4R-tau).

Epithelial–mesenchymal plasticity (EMP) 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 gene regulatory networks (GRNs) underlying EMP have yielded valuable insights into the dynamics of E and M phenotypes.

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 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 be contributing to their LLPS. We recently showed, using computational studies and designed proteins, that CC domains can facilitate LLPS through specific interactions between the CC domains themselves, meaning that each CC was designed to interact only with a subset of other CCs in the system.

We would like to thank all the reviewers who have donated their time and expertise to review papers submitted to Biophysical Journal. The list includes reviewers who served between November 1, 2024, and October 31, 2025.

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 have emerged as powerful tools for modeling macromolecular structures and interactions, offering faster and more cost-effective alternatives to experimental techniques.

The intercalated disc (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 study, we expand our previous finite element mesh framework to produce a more physiologically realistic representation of the ID, incorporating spatially heterogeneous gap junctions and multiple ion and ionic current dynamics.

The conformational variability of RNA duplexes with internal loop 5’GAGU/3’UGAG was investigated by nuclear magnetic resonance spectroscopy (NMR) and all-atom molecular dynamics simulations (MD). 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∗ and G6-G4∗ base pairs closing the loop. A minor conformation also existed with G-U pairs with a bifurcated hydrogen bond and A-G pairs with a single hydrogen bond (II).

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 outer-hair-cell bundles remain under debate and how adaptation works at physiologically-relevant frequencies is unclear.

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 of this machinery remain poorly understood. Here, we develop a three-dimensional model to systematically investigate the dynamic mechanical responses of spindle positioning machinery.

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 the effects of pulling direction and structural asymmetry, we simulated the two different fibrinogen molecules present in the crystallographic unit cell.

Cell and extracellular matrix (ECM) interactions are essential for maintaining tissue function and homeostasis. Changes in the biochemical or mechanical properties of the ECM 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 between fibroblasts and collagen in 3D hydrogels. We quantitatively measured changes in collagen branch number and junctions in 3D hydrogels using confocal reflectance microscopy and existing analysis protocols.