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Red blood cell (RBC) deformability is critical for in vivo tissue oxygenation and has been studied in ideal, canonical flows. In vitro frameworks are needed to study RBC deformation in more complex flows than those studied previously, as complex hemodynamics are common in blood-wetted medical devices and valvular pathologies. In this study, pseudo-3-dimensional RBC deformation and orientation angles are investigated in vitro in a microfluidic sudden expansion under two viscosity conditions (2.05, 4.17 cP) and three flow rates (100, 200, and 400 μL/min).

SIGNIFICANCEThe mean squared displacement (MSD) is a cornerstone in the analysis of diffusion processes in complex media. When the system is heterogeneous and, in particular, when single-particle trajectories are short, it is essential to extract maximal information from each measured trajectory. This is typically done by time-averaging squared increments and examining the scaling of the time-averaged MSD in log–log space. However, classical regression methods perform poorly in this setting because time-averaging introduces correlations aggravated by those inherent to anomalous diffusion.

Elucidating molecule-membrane interactions within bacterial cell walls is essential for understanding bacteria proliferation in the environment and developing effective therapeutics. Quantitative measurements of molecular adsorption and transport have been reported for individual membrane layers in Gram-negative bacteria, yet no analogous investigation exists for Gram-positive bacteria, which feature a substantially different cell wall architecture. In this work, we employed time-resolved second harmonic light scattering to quantify the adsorption and transport kinetics of a small antimicrobial cation, malachite green, at each of the surface layer (SL), peptidoglycan mesh (PM), and cytoplasmic membrane (CM) within the cell walls of three Gram-positive organisms: Lysinibacillus sphaericus, which possesses a canonical crystalline S-layer, and Bacillus subtilis and Lacticaseibacillus rhamnosus, whose outermost cell wall barriers are composed of surface-associated proteins and teichoic acids.

The binding of the ATP-bound form of kinesin-1 to a microtubule composed of the full-sequence of αβ-tubulin heterodimers (MT) and one composed of heterodimers with the disordered C-terminal tails deleted (ΔCTT-MT) was studied experimentally by single-molecule landing rate measurements and theoretically by coarse-grained molecular dynamics simulations. Theoretical models of MTs and ΔCTT-MTs comprised a total of 260 αβ-tubulin heterodimers each. The initial structure of the kinesin dimer was modeled with AlphaFold.

Microtubule dynamic instability—the stochastic switching between growth, shortening, and pausing—is essential for cytoskeletal organization and cellular function. Despite decades of experimental and theoretical work, its molecular mechanism remains unresolved. In this review, we organize existing models based on their underlying conceptual framework and physical assumptions. We first discuss GTP-cap-based models, including stochastic GTP-cap models, mechanical-cap models, and lattice-as-allosteric-effector models, highlighting how different microscopic assumptions and computational implementations lead to distinct explanations of dynamic-instability processes, especially catastrophe.

Voltage-sensitive dyes (VSDs) are frequently used to measure electrostatic potentials across (cell) membranes. Their use is based on the observed linear correlation between the second harmonic (SH) emission and an applied transmembrane potential. However, this intensity-to-potential conversion implicitly assumes a single, fixed dye orientation and a constant surface number density in the membrane, both taken to be independent of the local molecular environment. Here, we investigate whether these assumptions hold by imaging the SH response of a voltage-sensitive dye (FM4-64) in giant unilamellar vesicles (GUVs).

There are a large class of enveloped viruses that utilize sophisticated fusion mechanisms as a precursor to enter host cells. In SARS-Cov-2 the S2 domain of the S protein contains the fusion peptide (FP), which is believed to be central to the inter-membrane fusion machinery. However, the microscopic parameters that drive enhanced fusogenicity of the SARS-CoV-2 FP on realistic complex cellular membranes, leading to the observed virulence and fatality due to SARS-CoV-2 infection remains unclear. In this report, we identify the correlation between SARS-CoV-2 FP conformational and multi-phase cellular membrane dynamical heterogeneity, using existing and new membranotropic parameters, that drives enhanced SARS-CoV-2 FP fusogenicity.

Epithelial tissues are often exposed to cyclic deformations in their physiological environment. Maintenance of mechanical integrity relies on intercellular adhesion proteins which link neighbouring cells and transmit forces across the cellular network. The stability of these intercellular adhesion complexes is therefore critical for tissue strength. Under sustained stress, failure of intercellular adhesion complexes leads to damage accumulation that progressively weakens the material and ultimately causes failure at the tissue scale.

Accumulation of amyloid-β (Aβ) peptides and Tau proteins in the brain is a hallmark of neurodegeneration. Such build-up forms Aβ plaques and Tau neurofibrillary tangles, both of which are associated with synaptic loss, cognitive decline, and reduced cerebral blood flow in Alzheimer’s disease (AD). Two ion channels in brain capillary endothelial cells (ECs)—the inwardly rectifying potassium channel Kir2.1 and the mechanosensitive channel Piezo1—are critical regulators of cerebral blood flow, and both display impaired activity in AD.

Viral capsids are metastable assemblies whose large-scale dynamics enable critical steps in infection, including the exposure of internal protein segments that interact with host membranes. Resolving the mechanisms underlying these transitions remains challenging because they involve rare, cooperative motions distributed across entire viral particles. Here, we develop a full-capsid structure-based molecular dynamics framework to investigate infection-relevant dynamics in the T=3 Flock House virus capsid, a model non-enveloped RNA virus.

The frameshifting stimulatory element (FSE) of SARS-CoV-2 regulates programmed −1 ribosomal frameshifting, a process critical for viral protein synthesis, which has garnered attention as a potential antiviral target. In SARS-CoV-2, a 3-stem H-type pseudoknot has been widely recognized as the primary structure stimulating −1 frameshifting. However, both experimental and computational studies have revealed that the FSE is structurally heterogeneous and can adopt alternative structures. While this conformational plasticity is believed to play a central role in modulating frameshifting efficiency, transition pathways between these alternative FSE structures have remained poorly understood.

Predicting favorable protein-peptide binding events remains a central challenge in biophysics, with continued uncertainty surrounding how nonlocal effects shape the global energy landscape. Here, we introduce peripheral surface information (PSI) entropy, SΨ, a quantitative measure of the statistical variability in apolar and charged non-interacting surface (NIS) proportions across conformational ensembles. Within the Gibbs free-energy relation ΔG = ΔH − TΔS, SΨ is proposed as a computationally tractable entropic proxy rather than a direct thermodynamic observable or stand-alone estimator of binding affinity.