Assembly of tight junction belts by ZO1 surface condensation and local actin polymerization.

Tight junctions play an essential role in sealing tissues, by forming belts of adhesion strands around cellular perimeters. Recent work has shown that the condensation of ZO1 scaffold proteins is required for tight junction assembly. However, the mechanisms by which junctional condensates initiate at cell-cell contacts and elongate around cell perimeters remain unknown.

Empirical methods that provide physical descriptions of dynamic cellular processes.

We review empirical methods that can be used to provide physical descriptions of dynamic cellular processes during development and disease. Our focus will be nonspatial descriptions and the inference of underlying interaction networks including cell-state lineages, gene regulatory networks, and molecular interactions in living cells. Our overarching questions are: How much can we learn from just observing? To what degree is it possible to infer causal and/or precise mathematical relationships from observations? We restrict ourselves to data sets arising from only observations, or experiments in which minimal perturbations have taken place to facilitate observation of the systems as they naturally occur.

A cytokinetic ring-driven cell rotation achieves Hertwig's rule in early development.

Hertwig's rule states that cells divide along their longest axis, usually driven by forces acting on the mitotic spindle. Here, we show that in contrast to this rule, microtubule-based pulling forces in early embryos align the spindle with the short axis of the cell. We combine theory with experiments to reveal that in order to correct this misalignment, inward forces generated by the constricting cytokinetic ring rotate the entire cell until the spindle is aligned with the cell's long axis.

Glycolic acid and D-lactate-putative products of DJ-1-restore neurodegeneration in FUS - and SOD1-ALS.

Amyotrophic lateral sclerosis (ALS) leads to death within 2-5 yr. Currently, available drugs only slightly prolong survival. We present novel insights into the pathophysiology of (SOD1)- and in particular (FUS)-ALS by revealing a supposedly central role of glycolic acid (GA) and D-lactic acid (DL)-both putative products of the Parkinson's disease associated glyoxylase DJ-1.

Axis convergence in C. elegans embryos.

Embryos develop in a surrounding that guides key aspects of their development. For example, the anteroposterior (AP) body axis is always aligned with the geometric long axis of the surrounding eggshell in fruit flies and worms. The mechanisms that ensure convergence of the AP axis with the long axis of the eggshell remain unresolved.

Mass Balance Imaging: A Phase Portrait Analysis for Characterizing Growth Kinetics of Biomolecular Condensates.

Biomolecular condensation has emerged as a key organizing principle governing the formation of membraneless cellular assemblies. Revealing the mechanism of formation of biomolecular condensates requires the quantitative examination of their growth kinetics. Here, we introduce mass balance imaging (MBI) as a general method to study compositional growth dynamics based on fluorescent images of multicomponent clusters.

A condensate dynamic instability orchestrates actomyosin cortex activation.

A key event at the onset of development is the activation of a contractile actomyosin cortex during the oocyte-to-embryo transition. Here we report on the discovery that, in Caenorhabditis elegans oocytes, actomyosin cortex activation is supported by the emergence of thousands of short-lived protein condensates rich in F-actin, N-WASP and the ARP2/3 complex that form an active micro-emulsion. A phase portrait analysis of the dynamics of individual cortical condensates reveals that condensates initially grow and then transition to disassembly before dissolving completely.

Orchestrating nonmuscle myosin II filament assembly at the onset of cytokinesis.

Contractile forces in the actomyosin cortex are required for cellular morphogenesis. This includes the invagination of the cell membrane during division, where filaments of nonmuscle myosin II (NMII) are responsible for generating contractile forces in the cortex. However, how NMII heterohexamers form filaments in vivo is not well understood.

Co-condensation of proteins with single- and double-stranded DNA.

SignificanceBiomolecular condensates are intracellular organelles that are not bounded by membranes and often show liquid-like, dynamic material properties. They typically contain various types of proteins and nucleic acids. How the interaction of proteins and nucleic acids finally results in dynamic condensates is not fully understood.

Thermal fluctuations assist mechanical signal propagation in coiled-coil proteins.

Recently, it has been shown that the long coiled-coil membrane tether protein early endosome antigen 1 (EEA1) switches from a rigid to a flexible conformation upon binding of a signaling protein to its free end. This flexibility switch represents a motorlike activity, allowing EEA1 to generate a force that moves vesicles closer to the membrane they will fuse with. It was hypothesized that the binding-induced signal could propagate along the coiled coil and lead to conformational changes through the localized domains of the protein chain that deviate from a perfect coiled-coil structure.

A hydraulic instability drives the cell death decision in the nematode germline.

Oocytes are large cells that develop into an embryo upon fertilization. As interconnected germ cells mature into oocytes, some of them grow-typically at the expense of others that undergo cell death. We present evidence that in the nematode , this cell-fate decision is mechanical and related to tissue hydraulics.

CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left-right symmetry breaking.

Proper left-right symmetry breaking is essential for animal development, and in many cases, this process is actomyosin-dependent. In embryos active torque generation in the actomyosin layer promotes left-right symmetry breaking by driving chiral counterrotating cortical flows. While both Formins and Myosins have been implicated in left-right symmetry breaking and both can rotate actin filaments in vitro, it remains unclear whether active torques in the actomyosin cortex are generated by Formins, Myosins, or both.

Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome.

The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis.

HP1 proteins compact DNA into mechanically and positionally stable phase separated domains.

In mammals, HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here, we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories.

Regionalized tissue fluidization is required for epithelial gap closure during insect gastrulation.

Many animal embryos pull and close an epithelial sheet around the ellipsoidal egg surface during a gastrulation process known as epiboly. The ovoidal geometry dictates that the epithelial sheet first expands and subsequently compacts. Moreover, the spreading epithelium is mechanically stressed and this stress needs to be released.

Cell lineage-dependent chiral actomyosin flows drive cellular rearrangements in early development.

Proper positioning of cells is essential for many aspects of development. Daughter cell positions can be specified via orienting the cell division axis during cytokinesis. Rotatory actomyosin flows during division have been implied in specifying and reorienting the cell division axis, but how general such reorientation events are, and how they are controlled, remains unclear.

Guiding self-organized pattern formation in cell polarity establishment.

Spontaneous pattern formation in Turing systems relies on feedback. Patterns in cells and tissues however often do not form spontaneously, but are under control of upstream pathways that provide molecular guiding cues. The relationship between guiding cues and feedback in controlled biological pattern formation remains unclear.

Publisher Correction: Attachment of the blastoderm to the vitelline envelope affects gastrulation of insects.

In this Letter, the sentence starting: 'For instance, Tribolium and Drosophila inflated are direct targets of the mesoderm…' has been corrected online; see accompanying Amendment.

Attachment of the blastoderm to the vitelline envelope affects gastrulation of insects.

During gastrulation, physical forces reshape the simple embryonic tissue to form the complex body plans of multicellular organisms. These forces often cause large-scale asymmetric movements of the embryonic tissue. In many embryos, the gastrulating tissue is surrounded by a rigid protective shell.

Aurora A depletion reveals centrosome-independent polarization mechanism in .

How living systems break symmetry in an organized manner is a fundamental question in biology. In wild-type zygotes, symmetry breaking during anterior-posterior axis specification is guided by centrosomes, resulting in anterior-directed cortical flows and a single posterior PAR-2 domain. We uncover that zygotes depleted of the Aurora A kinase AIR-1 or lacking centrosomes entirely usually establish two posterior PAR-2 domains, one at each pole.

Morphogenetic degeneracies in the actomyosin cortex.

One of the great challenges in biology is to understand the mechanisms by which morphogenetic processes arise from molecular activities. We investigated this problem in the context of actomyosin-based cortical flow in zygotes, where large-scale flows emerge from the collective action of actomyosin filaments and actin binding proteins (ABPs). Large-scale flow dynamics can be captured by active gel theory by considering force balances and conservation laws in the actomyosin cortex.

Protein Dynamics in Complex DNA Lesions.

A single mutagen can generate multiple different types of DNA lesions. How different repair pathways cooperate in complex DNA lesions, however, remains largely unclear. Here we measured, clustered, and modeled the kinetics of recruitment and dissociation of 70 DNA repair proteins to laser-induced DNA damage sites in HeLa cells.