Branching, crosslinking and decentralization of microtubules accelerates intracellular assembly Wednesday, August 20, 2025 Before cell division, mitotic spindle is assembled from chromosomes and centrosomes. After the cell division, Golgi organelles assemble from multiple vesicles scattered across daughter cells. These are among many other examples of intracellular assembly of vesicles, organelles and chromosomes made possible by dynamic microtubules. The most prominent microtubule networks are centrosome-focused asters that ‘search’ for the vesicles and chromosomes, but there are also microtubules originating from the vesicles and chromosomes, raising the question whether a coordination between multiple microtubule networks optimizes the assembly process. Read more
Bayesian analysis and efficient algorithms for single-molecule fluorescence data and step counting Wednesday, August 20, 2025 With the growing adoption of single-molecule fluorescence experiments, there is an increasing demand for efficient statistical methodologies and accurate analysis of the acquired measurements. Existing analysis frameworks, such as those that use kinetic models, often rely on strong assumptions on the dynamics of the molecules and fluorophores under study that render them inappropriate for general purpose step counting applications, especially when the systems of study exhibit uncharacterized dynamics. Read more
Vesicle tension in porous membranes: aspiration, spreading, and tube extraction Monday, August 18, 2025 We review recent theoretical and experimental advances in understanding the mechanical tension of porous vesicles. Focusing on three key deformation processes, aspiration, spreading, and tube extrusion, we show how membrane porosity introduces novel timescales and feedback mechanisms that alter vesicle behavior. In particular, we highlight how tube extrusion from porous membranes demonstrates the vesicle’s ability to regulate internal volume and dynamically modulate membrane tension. This regulation enables the sustained elongation of membrane tubes under milder mechanical conditions than those required for non-porous vesicles. Read more
Prediction of αIIbβ3 integrin structures along its minimum free energy activation pathway Monday, August 18, 2025 The adhesion protein integrin is a transmembrane heterodimer that plays a pivotal role in cellular processes such as cell signaling and cell migration. To execute its function, integrin undergoes extensive conformational changes from a bent-closed to an extended-open state. Resolving the structures across these changes remains a challenge with both experimental and computational methods, but is crucial for understanding the activation mechanism of integrin. We address this challenge for the platelet integrin αIIbβ3 by employing finite temperature string method with structures of the images along the initial guess path generated by a multiscale data-driven framework. Read more
Direct mechanical communication of cellular to nuclear shape in oocytes Monday, August 18, 2025 The mechanical properties of the cytoplasm and nucleoplasm are crucial for the correct and robust functioning of a cell and play a key role in understanding how mechanical signals are transferred to the nucleus. Here, we demonstrate remarkable shape mimicry between the cellular and nuclear shape of oocytes, following the externally applied deformation without direct contact between the cell cortex and the nucleus. This effect arises from a surprisingly soft and fluid-like nucleoplasm that barely resists external strain, while the viscoelastic cytoplasm drives shape transmission. Read more
Unraveling the Conformational Landscape of Amyloid Precursor Protein Intracellular Domain Thursday, August 14, 2025 The amyloid precursor protein intracellular domain (AICD), a cleavage product of Amyloid Precursor Protein (APP) implicated in Alzheimer’s disease and Amyloid Lateral Sclerosis (ALS), is a functionally important but structurally elusive intrinsically disordered protein (IDP). In this study, we investigate the conformational ensemble of a 35-residue AICD segment encompassing the conserved YENPTY motif using molecular dynamics (MD) simulations, small-angle X-ray scattering (SAXS), circular dichroism (CD), and Nuclear Magnetic Resonance (NMR) data. Read more
Time-dependent active force drives periodic reversal in collective cell migration Wednesday, August 13, 2025 Collective cell migration is prevalent in the processes of embryo development, wound healing, and cancer metastasis across various space and time scales. While various motion modes have been identified, their relationships with single cell motility and the underlying mechanisms remain poorly understood. In this study, we develop an active vertex model to investigate the spatiotemporal behavior of collective cells confined in annulus domain, accounting for the polarity memory effect of individual cells and the impact of confinement size. Read more
Combinatorial Sample-and Back-Focal-Plane (BFP) Imaging. Pt. I: Instrument and acquisition parameters affecting BFP images and their analysis Monday, August 11, 2025 The back-focal plane (BFP) of a high-numerical aperture objective contains the fluoro-phore radiation pattern, which encodes information about the axial fluorophore position, molecular orientation and the local refractive index of the embedding medium. BFP image acquisition and analysis are common to conoscopy, k-space imaging, supercritical-angle fluorescence (SAF) and single-molecule detection, but they are rarely being used in biological fluorescence. This work addresses a critical gap in quantitative microscopy by enabling reliable, real-time BFP imaging under low-light conditions and/or short exposure times, typical of biological experiments. Read more
Role of ionic electrodiffusion and ephaptic coupling in cardiac dynamics Monday, August 11, 2025 Cardiac myocytes coordinate the heart contractions through electrical signaling, facilitated by gap junctions (GJs) in the intercalated disc (ID). GJs provide low-resistance pathways for electrical propagation between myocytes, acting as the main mechanism for electrical communication in the heart. However, studies show that conduction can persist in the absence of GJs. For instance, GJ knockout mice still display slow and discontinuous electrical propagation, suggesting the presence of alternative communication mechanisms. Read more
Geometry effects on protein mobility in a synapse Friday, August 8, 2025 It is generally assumed that synaptic function requires a tight regulation of the mobility and localisation of synaptic proteins. Evidence for this hypothesis has been difficult to gather. Protein mobility can be measured via fluorescence recovery after photobleaching (FRAP), but the interpretation of the results remains challenging. In this study, we perform in silico FRAP experiments to study the effects of the synaptic geometry and/or protein binding to synaptic vesicles on protein mobility. We matched simulations with published FRAP data for 40 different synaptic proteins, to obtain diffusion coefficients, vesicle binding rates, and binding times. Read more
Quantifying the potential of Thermal Highways to facilitate Long Range Proton Transport in Enzymes Friday, August 8, 2025 Proton transport in enzymes is often portrayed as a purely static, hydrogen–bond–mediated relay, yet this view neglects how ultrafast vibrational coherence within the protein fold can mechanically drive long-range transfer. Here, we introduce the vibrational-entropy flux tensor to identify thermal highways—evolutionarily conserved networks of residues whose synchronized terahertz-frequency phonons transiently compress donor–acceptor distances. Using parameter-free coarse-grained elastic-network models of [FeFe]-hydrogenase, we show that these highways boost quantum-tunneling probabilities by 10–100× (depending on mode frequency), directly linking picosecond-scale dynamics to increased proton flux. Read more