In order to proliferate, bacteria must remodel their cell wall at the division site. The division process is driven by the enzymatic activity of peptidoglycan (PG) synthases and hydrolases around the constricting Z-ring. PG remodelling is regulated by de- and re-crosslinking enzymes, and the directing constrictive force of the Z ring. We introduce a model that is able to reproduce correctly the shape of the division site during the constriction and septation phase of E. coli. The model represents mechanochemical coupling within the mathematical framework of morphoelasticity. It contains only t ..read more

The establishment and interpretation of the concentration distribution of the morphogen Bicoid (Bcd) is considered crucial for the successful embryonic development of fruit flies. However, the biophysical mechanisms behind the timely formation and subsequent interpretation of this prototypical morphogenetic system by its target genes are not yet completely understood. Recently a discrete time, one-dimensional quantum walk model of Bcd gradient formation has been successfully used to explain the observed multiple dynamic modes of the Bcd system. However, the question of its precise interpretati ..read more

Recent advances in hydrodynamic theory have revealed the severe effect of periodic boundary conditions (PBCs) on the diffusive dynamics of lipid membranes in molecular dynamics simulations. Even when accounting for PBC effects, the corrected lipid diffusion coefficients often severely overshoot the experimental estimates. Here, we investigate the underlying reasons for the exaggerated dynamics, and suggest potential ways for improvement. To this end, we examine the diffusion of four lipid types in both bilayers and monolayers using the CHARMM36 force field. We account for PBC effects using the ..read more

Cross-linking mass spectrometry (XL-MS) enables the mapping of protein-protein interactions on the cellular level. When applied to all compartments of mitochondria, the sheer number of cross-links and connections can be overwhelming, rendering simple cluster analyses convoluted and uninformative. To address this limitation, we integrate the XL-MS data, 3D electron microscopy data, and localization annotations with a supra coarse-grained molecular dynamics simulation to sort all data, making clusters more accessible and interpretable. In the context of mitochondria, this method, through a total ..read more

Collection of myosin motors and actin filaments can self-assemble into submicrometric clusters under the regulation of RhoA. Emergent dynamics of these clusters have been reported in a variety of morphogenetic systems, ranging from Drosophila to acto-myosin assays in vitro. In single cell cytokinetic rings, acto-myosin clusters are associated with stress generation when radial and transport when tangential with respect to the ring closure. Here, we show that these phenomena hold true for acto-myosin multi-cellular rings during wound closure in epithelial monolayers. We assessed the activity of ..read more

Advancing single-frame imaging techniques beyond the diffraction limit and upgrading traditional wide-field or confocal microscopes to super-resolution (SR) capabilities are greatly sought after by biologists. While enhancing image resolution by deconvolving noise-free images is beneficial, achieving a noise-free image that maintains the distribution of signal intensity poses a challenge. We first developed a denoising method utilizing reversibly switchable fluorescent proteins through synchronized signal switching (3S). Additionally, we introduced a denoising neural network technique, 3Snet ..read more

Hyperuricemia is a condition when uric acid, a waste product of purine metabolism, accumulates in the blood. Untreated hyperuricemia can lead to crystal formation of monosodium urate in the joints, causing a painful inflammatory disease known as gout. These conditions are associated with many other diseases and affect a significant and increasing proportion of the population. The human urate transporter 1 (URAT1) is responsible for the reabsorption of ~90% of uric acid in the kidneys back into the blood, making it a primary target for treating hyperuricemia and gout. Despite decades of researc ..read more

Voltage-gated sodium (Nav) channels are pivotal for cellular signaling and mutations in Nav channels can lead to excitability disorders in cardiac, muscular, and neural tissues. A major cluster of pathological mutations localizes in the voltage-sensing domains (VSDs), resulting in either gain-of-function (GoF), loss-of-function (LoF) effects, or both. However, the mechanism behind this functional divergence of mutations at equivalent positions remains elusive. Through hotspot analysis, we identified three gating charges (R1, R2, and R3) as major mutational hotspots in VSDs. The same amino-acid ..read more

The point mutation N642H of the signal transducer and activator of transcription 5B (STAT5B) protein is associated with aggressive and drug-resistant forms of leukemia. This mutation is thought to promote cancer due to hyperactivation of STAT5B caused by increased stability of the active, parallel dimer state. However, the molecular mechanism leading to this stabilization is not well understood as there is currently no structure of the parallel dimer. To investigate the mutations mechanism of action, we conducted extensive all-atom molecular dynamics simulations of multiple oligomeric forms of ..read more

A proteins energy landscape, all the accessible conformations, their populations, and their dynamics of interconversion, is encoded in its primary sequence. While we have a good understanding of how a proteins primary sequence encodes its native state, we have a much weaker understanding of how sequence encodes the kinetic barriers such as unfolding and refolding. Here we have looked at two subtiliase homologs from the Bacillus subtilis, Intracellular Subtilisin Protease 1 (ISP1) and Subtilisin E (SbtE) that are expected to have very different dynamics. As an intracellular protein, ISP1 has a ..read more