Articles Online Now

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.

A living cell is a nonequilibrium thermodynamic system where, nevertheless, a notion of local equilibria 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 a condition is fulfilled, one can control local variables and their gradients to theoretically describe the thermodynamic state of living systems at the micro- and nanoscale.

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 measure forces in populations of cells and to identify subsets within heterogeneous ensembles would enable to reveal and manipulate their intrinsic complexity.

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 sidechains and presents a specific ligand for protein bovine carbonic anhydrase II (bCA-II). To further understand the molecular forces and mechanism of the assembly and disassembly of P1, we developed a coarse-grained modeling framework for direct simulation of the dynamic polymer-unimer equilibrium of amphiphilic peptide nanoassembly.

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 (SzR4). In contrast, numerous structures of outward proton-pumping rhodopsins are available, posing challenges for broad structure-function comparisons and limiting the study of structural variations among inward proton pumps.

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 structure composed entirely of α-helices with an unstructured C-terminal region. Here, we combine site-directed mutagenesis and antimicrobial assays with AlphaFold2 modelling and molecular dynamics simulations to define the structural basis of GarC recognition of Man-PTS.