Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis.

Transforming growth factor β (TGF-β) signaling is a core pathway of fibrosis, but the molecular regulation of the activation of latent TGF-β remains incompletely understood. Here, we demonstrate a crucial role of WNT5A/JNK/ROCK signaling that rapidly coordinates the activation of latent TGF-β in fibrotic diseases. WNT5A was identified as a predominant noncanonical WNT ligand in fibrotic diseases such as systemic sclerosis, sclerodermatous chronic graft-versus-host disease, and idiopathic pulmonary fibrosis, stimulating fibroblast-to-myofibroblast transition and tissue fibrosis by activation of latent TGF-β.

A paintbrush for delivery of nanoparticles and molecules to live cells with precise spatiotemporal control.

Delivery of very small amounts of reagents to the near-field of cells with micrometer spatial precision and millisecond time resolution is currently out of reach. Here we present μkiss as a micropipette-based scheme for brushing a layer of small molecules and nanoparticles onto the live cell membrane from a subfemtoliter confined volume of a perfusion flow. We characterize our system through both experiments and modeling, and find excellent agreement.

High-Precision Protein-Tracking With Interferometric Scattering Microscopy.

The mobility of proteins and lipids within the cell, sculpted oftentimes by the organization of the membrane, reveals a great wealth of information on the function and interaction of these molecules as well as the membrane itself. Single particle tracking has proven to be a vital tool to study the mobility of individual molecules and unravel details of their behavior. Interferometric scattering (iSCAT) microscopy is an emerging technique well-suited for visualizing the diffusion of gold nanoparticle-labeled membrane proteins to a spatial and temporal resolution beyond the means of traditional fluorescent labels.

Lipid Dynamics in Membranes Slowed Down by Transmembrane Proteins.

Lipids and proteins, as essential components of biological cell membranes, exhibit a significant degree of freedom for different kinds of motions including lateral long-range mobility. Due to their interactions, they not only preserve the cellular membrane but also contribute to many important cellular functions as e.g.

Molecular crosstalk between Y5 receptor and neuropeptide Y drives liver cancer.

Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result of globally increasing risk factors including metabolic disorders, the incidence rates of HCC are still rising. However, the molecular hallmarks of HCC remain poorly understood.