Nanoscale Domains Govern Local Diffusion And Ageing Within Fused-In-Sarcoma Condensates
Imagine tiny, dynamic compartments within our cells, called biomolecular condensates, that act like bustling mini-factories, organizing essential molecules like RNA and proteins to carry out vital cellular tasks. For a long time, scientists have wondered how these factories precisely control the movement and interactions of their components, and what happens when these processes go awry, especially in diseases like Amyotrophic Lateral Sclerosis (ALS).
Recent groundbreaking research has shed light on this mystery by revealing the existence of “nanodomains” – incredibly small, distinct regions within these condensates. Think of these nanodomains as specialized workstations within the factory, each with its own unique environment and connections. It turns out that the movement of RNA and protein molecules is not random throughout the condensate, but rather confined within these specific nanodomains. This confinement dictates how long molecules stay in certain areas and how they interact, ultimately governing the condensate’s function.
What’s even more fascinating is how these nanodomains play a role in the “aging” of condensates, a process where they can transition from a liquid-like state to a more solid, potentially harmful one. In the context of ALS, where a protein called FUS forms problematic condensates, these nanodomains were observed to reposition as the condensates aged. This repositioning actually encourages the formation of harmful protein fibers, a hallmark of the disease, particularly at the condensate’s edges. Surprisingly, some existing ALS drugs were found to enhance these aging-induced changes in the nanodomains.
This discovery fundamentally changes our understanding of how these cellular compartments work. By showing that these tiny internal structures dictate molecular organization and influence disease-related changes, it opens up new avenues for understanding and potentially treating neurodegenerative conditions.
Source: link to paper