BJ Articles Ahead of Print

Cholesterol is essential to the formation of phase separated lipid domains in membranes. Lipid domains can exist in different thermodynamic phases depending on the molecular composition, and play significant roles in determining structure and function of membrane proteins. We investigate the role of cholesterol in the structure and dynamics of ternary lipid mixtures displaying phase separation using Molecular Dynamics simulations, employing a physiologically-relevant span of cholesterol concentration.

During asymmetric division of Caenorhabditis elegans zygote, to properly distribute cell fate determinants, the mitotic spindle is asymmetrically localized by a combination of centering and cortical pulling microtubule-mediated forces, the dynamics of the latter being regulated by mitotic progression. Here we show a novel and additional regulation of these forces by spindle position itself. For that, we observed the onset of transverse spindle oscillations which reflects the burst of anaphase pulling forces.

Dimeric motor proteins, kinesin-1, cytoplasmic dynein-1, and myosin-V, move stepwise along microtubules and actin filaments with a regular step size. The motors take backward as well as forward steps. The step ratio r and dwell time τ, which are the ratio of the number of backward steps to the number of forward steps and the time between consecutive steps, respectively, were observed to change with the load. To understand the movement of motor proteins, we constructed a unified and simple mathematical model to explain the load dependencies of r and of τ measured for the above three types of motors quantitatively.

Investigations over half a century have indicated that mechanical forces induce neurite growth - with neurites elongating at a rate of 0.1-0.3 μm h-1 pN-1, when mechanical force exceeds a threshold, with this being identified as 400-1000 pN for neurites of PC12 cells. In this communication, we demonstrate that neurite elongation of PC12 cells proceeds at the same previously identified rate, on application of mechanical tension of ∼ 1 pN, which is significantly lower than the force generated in-vivo by axons and growth cones.

Actomyosin contractility regulates various biological processes including cell migration and cytokinesis. The cell cortex underlying the membrane of eukaryote cells exhibits dynamic contractile behaviors facilitated by the actomyosin contractility. Interestingly, the cell cortex shows reversible aggregation of actin and myosin called ‘pulsed contraction’ in diverse cellular phenomena, such as embryogenesis and tissue morphogenesis. While contractile behaviors of actomyosin machinery have been studied extensively in several in vitro experiments and computational studies, none of them successfully reproduced pulsed contraction observed in vivo.

The organization of chromatin in 30 nm fibers remains a topic of debate. Here we quantify the mechanical properties of the linker DNA and evaluate the impact of these properties on chromatin fiber folding. We extended a rigid base-pair DNA model to include (un-)wrapping of nucleosomal DNA and (un-)stacking of nucleosomes in one-start and two-start chromatin fibers. Monte Carlo simulations that mimic single-molecule force spectroscopy experiments of folded nucleosomal arrays reveal different stages of unfolding as a function of force and are largely consistent with a two-start folding for 167 and one-start folding for 197 nucleosome repeat length fibers.

Epithelial-to-mesenchymal transition (EMT) and maturation of collagen fibrils in the tumor microenvironment play a significant role in cancer cell invasion and metastasis. Confinement along fiber-like tracks enhances cell migration. To what extent and in what manner EMT further promotes migration in a microenvironment already conducive to migration is poorly understood. Here, we show that TGFβ-mediated EMT significantly enhances migration on fiber-like micropatterned tracks of collagen, doubling migration speed and tripling persistence relative to untreated mammary epithelial cells.

Mathematical models of fundamental biological processes play an important role in consolidating theory and experiments, especially if they are systematically developed, thoroughly characterized, and well tested by experimental data. In this work, we report a detailed bifurcation analysis of a mathematical model of the mammalian circadian clock network developed by Relogio et al. [16], noteworthy for its consistency with available data. Using one- and two-parameter bifurcation diagrams, we explore how oscillations in the model depend on the expression levels of its constituent genes and the activities of their encoded proteins.

AlkB homologue 5 (Alkbh5) is one of nine members of the AlkB family, which are non-heme Fe2+/α-ketoglutarate (αKG)-dependent dioxygenases that catalyze the oxidative demethylation of modified nucleotides and amino acids. Alkbh5 is highly selective for the N6-methyladenosine (m6A) modification, an epigenetic mark that has spawned significant biological and pharmacological interest, due to its involvement in important physiological processes, such as carcinogenesis and stem-cell differentiation. Herein, we investigate the structure and dynamics of human Alkbh5 in solution.

Compositional asymmetry between the leaflets of bilayer membranes modifies their phase behaviour, and is thought to influence other important features such as mechanical properties and protein activity. We address here how phase behaviour is affected by passive phospholipid flip-flop, such that the compositional asymmetry is not fixed. We predict transitions from “pre flip-flop” behaviour to a restricted set of phase equilibria that can persist in the presence of passive flip-flop. Surprisingly, such states are not necessarily symmetric.

During ribosomal translation, nascent polypeptide chains (NCs) undergo a variety of physical processes that determine their fate in the cell. This study utilizes a combination of arrest peptide (AP) experiments and coarse-grained molecular dynamics (CGMD) to measure and elucidate the molecular origins of forces that are exerted on NCs during co-translational membrane insertion and translocation via the Sec translocon. The approach enables deconvolution of force contributions from NC-translocon and NC-ribosome interactions, membrane partitioning, and electrostatic coupling to the membrane potential.

The lipidome of plant plasma membranes – enriched in cellular phospholipids containing at least one polyunsaturated fatty acid tails and a variety of phytosterols and phytosphingolipids – is adapted to significant abiotic stresses. But how mesoscale membrane properties of these membranes, such as permeability and deformability, which arise from their unique molecular compositions and corresponding lateral organization, facilitate response to global mechanical stresses is largely unknown. Here, using giant vesicles reconstituting mixtures of polyunsaturated lipids (Soy-PC), glucosylceramide (GlcCer), and sitosterol common to plant membranes, we find that the membranes adopt “janus-like” domain morphologies and display anomalous solute permeabilities.