Topic: liquid-liquid phase separation

Amino acids have long been used in biological and pharmaceutical formulations, but their stabilizing effects are often described only for particular proteins. This talk examines a broader mechanism: small molecules modify colloidal interactions in proteins, DNA and synthetic nanoparticles. Measurements of osmotic virial coefficients and potentials of mean force reveal consistent effects across these systems. A model of weakly interacting amino acids binding to patchy colloidal surfaces predicts experimentally measured dissociation constants; proline–lysozyme predictions and measurements agree

Diverse physical processes played important roles in the origin of life. I will review the origin of molecular homochirality, the growth of protocell membranes, and potential roles for liquid-liquid phase separation. I will then discuss the concept of functional information and its quantitative relationship with molecular function.

Living cells contain millions of enzymes and proteins, which carry out multiple reactions simultaneously. To optimize these processes, cells compartmentalize reactions in membraneless liquid condensates. Certain features of cellular condensates can be explained by principles of liquid-liquid phase separation studied in material science. However, biological condensates exist in the inherently out of equilibrium environment of a living cell, being driven by force-generating microscopic processes. These cellular conditions are fundamentally different than the equilibrium conditions of liquid-liqu

Intrinsically disordered proteins (IDPs), lack of a well-defined folded structure, have been recently shown to be critical to forming membrane-less organelles via liquid-liquid phase separation (LLPS). Due to the flexible conformations of IDPs, it could be challenging to investigate IDPs with solely experimental techniques. Computational models can therefore provide complementary views at several aspects, including the fundamental physics underlying LLPS and the sequence determinants contributing to LLPS. In this presentation, I will start with our coarse-grained computational framework tha

Memory and learning are significantly influenced by long-term changes in synaptic strength, though the exact molecular mechanisms remain unclear. The postsynaptic density (PSD) is a critical component for storing and organizing synaptic long-term changes. The PSD itself is organized into complex nano-clusters, which are modulated during synaptic plasticity. However, the underlying organizational principles yielding such changes and maintaining stability otherwise are still to a large degree unknown. Recent research assumes that liquid-liquid phase separation (LLPS) might be crucial for PSD for

Tau, is an intrinsically disordered protein crucial for stabilizing and polymerizing microtubules (MTs). However, in Alzheimer's disease (AD), Tau undergoes hyperphosphorylation, leading to its misfolding and detachment from MTs, forming droplets termed liquid-liquid phase separation (LLPS), believed to be a precursor to Tau aggregates. Despite being a biomarker for AD, the role of AT8 phosphorylation (S202, T205, and S208) in Tau spread and toxicity remains unclear. To address this issue, we generated Tau variants with different AT8 phosphorylation states: PTau 2A-, 208- (lacking AT8 phosphor

The transcription factor FOXP2 is a regulator of vocalization-, speech-, and language-related phenotypes in human and non-human species. The FOXP2 protein contains multiple domains including a DNA-binding forkhead domain, a zinc finger domain, a leucine zipper, and N-terminal polyglutamine (polyQ) repeats. We have recently found that the FOXP2 N-terminal polyQ region drives the liquid-liquid phase separation (LLPS) of the protein. FOXP2 LLPS is regulated by the evolutionary length variation of the polyQ repeats and has a role in modulating the transcriptional activity of the protein. The poten

Reactive oxygen species (ROS) play a central role in enhancing inhibitory signal transmission, thus extending their role beyond oxidative stress in disease and aging. However, the underlying molecular mechanisms mediating these functions have remained elusive. At inhibitory synapses, the scaffolding protein gephyrin clusters glycine and GABA type A receptors. Since gephyrin harbors multiple surface-exposed cysteines, we investigated the regulatory influence of ROS on gephyrin. We show that H2O2-induced oxidation of gephyrin cysteines triggered reversible, synaptic multimerization through disul

TDP-43 is the hallmark protein of several neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS). This RNA-binding protein can form membrane-less condensates through liquid-liquid phase separation (LLPS). This biophysical process is considered to contribute to the regulation of TDP-43 functions but the precise mechanisms governing TDP-43 LLPS and its implications in homeostasis as well as pathology remain incompletely understood.In this study, we aimed to elucidate the influence of RNA-binding on TDP-43 dynamics and localization in vivo. By applying confocal imaging workflow

Neurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within the presynaptic bouton of neurons. The ability of SVs to dynamically recycle while remaining clustered at the presynapse is unknown but suggests anchoring mechanisms that regulate SV function. One potential anchor is a family of phosphoproteins that interact with presynaptic SVs, called synapsins. Synapsins tightly bind SVs and form biomolecular condensates via liquid-liquid phase separation which can potentially help trap SVs at the presynapse. An alternative model for synapsin’s