Publications – RTG 3120 Biomolecular Condensates

Molecular dynamics investigation of polymer-decorated nanoparticles with co-nonsolvent

Mohamad Almedawar — Thu, 09 Oct 2025 09:42:38 +0000

A new study by Sommer and colleagues in the Journal of Chemical Physics investigates how polymer-decorated nanoparticles (PDNPs)—tiny particles coated with grafted polymer chains—undergo structural changes in mixed-solvent environments. Using detailed molecular dynamics simulations, the authors of the study entitled “Molecular dynamics investigation of polymer-decorated nanoparticles with co-nonsolvent: Structural transitions from isotropic layers to heterogeneous patches” reveal how the co-nonsolvency (CNS) effect—a phenomenon where adding a small amount of a secondary solvent can change overall solvent quality—induces dramatic transformations in PDNP morphology.

In good solvents, the grafted polymers form uniform, isotropic “brush-like” layers around the nanoparticle, completely covering its surface. As CNS concentration increases, the solvent becomes poorer, triggering a first-order phase transition in which these smooth polymer coatings collapse into heterogeneous patchy micelles.	© Copyright 2025 AIP Publishing LLC

This process is reversible: upon further increasing the better solvent’s proportion, the system undergoes a two-step reentry transition—first restoring angular uniformity and then expanding radially. The researchers use a quantitative descriptor, surface coverage (θ), which measures how much of the nanoparticle surface remains shielded by polymer. Tracking θ provides deep insight into these morphological transitions beyond traditional metrics like brush thickness.

A major finding is that PDNPs on curved (spherical) surfaces respond more sensitively and over broader parameter ranges than planar polymer brushes, making them better suited for practical applications. The simulations further demonstrate that these solvent-controlled structural changes can reversibly regulate the adsorption or exclusion of cargo nanoparticles(CNPs) based on size. Small CNPs can penetrate swollen brushes in good solvents, while larger ones adhere only when the polymer collapses into patches, enabling selective, tunable particle screening.

Impact:
This work provides a mechanistic framework for designing stimuli-responsive nanomaterials that can reversibly change surface properties and selectively interact with other particles—all through minimal solvent adjustments rather than temperature or pH changes. The results have promising implications for drug delivery systems, smart coatings, and nanoscale separation technologies, where environmental control and size-selectivity are critical

Citation:

Cheng-Wu Li, Holger Merlitz, Jens-Uwe Sommer; Molecular dynamics investigation of polymer-decorated nanoparticles with co-nonsolvent: Structural transitions from isotropic layers to heterogeneous patches. J. Chem. Phys. 7 October 2025; 163 (12): 124902. https://doi.org/10.1063/5.0295227

Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates

Mohamad Almedawar — Wed, 20 Aug 2025 13:15:24 +0000

A new study from the labs of Honigmann, Hyman, and Alberti in Dresden, in addition to colleagues in Texas A&M University, Mayo Clinic, Brown University, and Saint Louis University investigates the mechanism behind pathological outcomes of protein aggregation inside stress granules. The authors of the study entitled “Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates” and published in Cell in May, 2025, determined that aggregation of TAR DNA-binding protein 43 (TDP-43) is induced by two events, namely up-concentration of TDP-43 in stress granules beyond a threshold and oxidative stress and described the mechanism behind the observation. They use this new understanding to engineer TDP-43 variants resistant to aggregation in the cell.

Impact: The aggregation of TDP-43 in motor neurons is a hallmark of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Understanding the mechanisms leading to aggregation paves the path towards developing preventive and therapeutic strategies.

Citation:

Yan, X., Kuster, D., Mohanty, P., Nijssen, J., Pombo-García, K., Garcia Morato, J., Rizuan, A., Franzmann, T. M., Sergeeva, A., Ly, A. M., Liu, F., Passos, P. M., George, L., Wang, S.-H., Shenoy, J., Danielson, H. L., Ozguney, B., Honigmann, A., Ayala, Y. M., Fawzi, N. L., Dickson, D. W., Rossoll, W., Mittal, J., Alberti, S., & Hyman, A. A. (2025). Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates. Cell, 188(15), 4123-4140.e4118. https://doi.org/10.1016/j.cell.2025.04.039

Impact of Coiled-Coil Domains on the Phase Behavior of Biomolecular Condensates

Mohamad Almedawar — Wed, 20 Aug 2025 12:35:44 +0000

A new Study from the Harmon and Sommer Labs in ACS Macro Letters entitled ‘Impact of Coiled-Coil Domains on the Phase Behavior of Biomolecular Condensates’ addressed how the geometry and structure of folded domains impact condensate formation. They used coarse-grained simulations to determine that coiled-coil domains (CCDs) promote liquid–liquid phase separation (LLPS), while replacing the CCD with a flexible linker abolishes LLPS. CCDs must have a critical length to promote LLPS at low concentrations.

The results of this study offer a framework for designing synthetic condensates with tunable phase behaviors.

Citation:

Zhouyi He, Jens-Uwe Sommer, and Tyler S. Harmon. Impact of Coiled-Coil Domains on the Phase Behavior of Biomolecular Condensates. ACS Macro Letters 2025 14 (4), 413-419. DOI: 10.1021/acsmacrolett.4c00821

Researchers from Dresden and Barcelona reveal how glycolysis drives early embryonic cell decisions

Mohamad Almedawar — Wed, 09 Jul 2025 19:40:41 +0000

The studies, published in CellStemCell with the participation of RTG 3120 PI Miki Ebisuya, uncover the instructive potential of glycolysis. Read the press coverage and publications for more:

https://www.embl.org/news/science-technology/metabolism-shapes-life/
https://www.mpi-cbg.de/news-outreach/news-media/article/metabolism-shapes-life
Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model. Cell Stem Cell, 16 April, 2025. https://doi.org/10.1016/j.stem.2025.03.012
Glycolytic activity instructs germ layer proportions through regulation of Nodal and Wnt signaling, Cell Stem Cell (2025). https://doi.org/10.1016/j.stem.2025.03.011

Molecular Assembly Lines in Active Droplets

Mohamad Almedawar — Wed, 30 Nov 2022 18:08:37 +0000

Cells assemble structures that have lots of molecules. How can such complicated structures be reliably assembled? We propose that cells could be organizing an assembly line process for the construction. We show how this could be organized inside droplets. In this video we explain our recent work published in PRL. Check out the paper for more info: https://journals.aps.org/prl/abstract…

Prepared by Mariona Esquerda Ciutat from the Hyman and Jülicher labs in Dresden.

The key role of solvent in condensation: Mapping water in liquid-liquid phase-separated FUS

Mohamad Almedawar — Tue, 06 Apr 2021 08:09:39 +0000

What drives the formation of biomolecular condensates from proteins in water? The Adams group, in collaboration with colleagues from Ruhr-University Bochum, Germany, measured the thermodynamic forces leading to the expulsion of water from condensates as they form through protein-protein interactions. the results are published in the Biophysical Journal. Read more.

Scheme showing the proposed water-mediated contribution of FUS to LLPS. Formation of phase-separated droplets is supported by an increase in tetrahedral coordination of water molecules (bound water; thick black) and minimization of less favorable water interactions (wrap water; red).

The ALS-Associated FUS (P525L) Variant Does Not Directly Interfere with Microtubule-Dependent Kinesin-1 Motility

snmadmin — Sun, 28 Feb 2021 13:00:44 +0000

The Diez lab, in collaboration with the Hermann lab in Rostock, Germany, have utilised an in vitro microtubule gliding motility assay to study deficient intracellular transport in motor neurons. The findings exclude a role of mutations in the phase-separating FUS protein, known to be mutated in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). in The study was published in the International Journal of Molecular Sciences as part of the Special Issue Molecular Mechanisms of Aging-Related Neurodegenerative Diseases.

Reconstituting axonal transport in vitro

Cytoskeletal organization through multivalent interactions

snmadmin — Mon, 15 Jun 2020 12:46:53 +0000

Stefan Diez and collaborators Zdenek Lansky and Marcus Braun from the Institute of Biotechnology of the Czech Academy of Sciences, Czech Republic, published an Opinion article emphasizing the role of multivalent interactions cytoskeletal phenomena including (1) the generation of entropic forces by filament crosslinkers, (2) processivity of molecular motors, (3) spatial sorting of proteins, and (4) concentration-dependent unbinding of filament-associated proteins. The article was published in the Journal of Cell Science.

Consequences of multivalent interactions on ligand–receptor interaction kinetics

Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes

snmadmin — Tue, 02 Jul 2019 12:59:13 +0000

The Diez and Hyman labs, in collaboration with the Lansky and Braun lab at the Institute of Biotechnology of the Czech Academy of Sciences, Czech Republic, published a study on the role of phase separation of the intrinsically disordered Tau protein in regulating the activity of motor proteins and severing enzymes on microtubules. The study, published in Nature Cell Biology demonstrated using in vitro protein reconstitution that Tau protects microtubules from degradation by forming reversible cohesive islands.

Tau islands constitute a protective layer around microtubules