The main seat of the eukaryotic cell is the nucleus, and most of the cell’s information and instructions are stored there in the form of DNA (deoxyribonucleic acid). Twisted, coiled, and bundled two-meter long DNA strands with protein molecules form the chromatin fibers within the nucleus. For years, scientists have been interested in how these ingredients are regulated. How can proteins essential in biochemical reactions move efficiently within a nucleus filled with DNA? Recent studies have finally solved the puzzle. The results you describe in detail have been published in Journal of Physical Chemistry Letters On December 21, 2020.
Molecules in a crowded nucleus
The nucleus of each cell conceals a two-meter-long chain of an amazing and unique molecule: DNA. Besides the various histones and related proteins, DNA builds a chromatin frame filled with a viscous liquid that shows excellent diversity in molecular structure. For decades, the mobility of particles in the nucleus has not been sufficiently explored, but recent developments have changed this status quo. Thanks to in-depth research by a group of researchers from the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) led by Professor Robert Ho West, the transport of particles at long scales from one to tens of nanometers in the nucleus is detailed in detail.
Large molecular store
Due to its small size, one can assume that the nucleus has a simple structure and random molecular distribution. This is by no means the case. The kernel has an incredibly complex and tuned layout. DNA is nothing like the messy tangle of spaghetti. They are efficiently packaged in compact structures. Even the nanoscale viscosity of the nucleus determines the mobility of individual bodies inside. For a better visualization of how well all of this is organized, The Kernel can be described as a supermarket. The chromatin fibers act like shelves, containing a variety of necessary genetic information (such as DNA) just like store shelves full of products. These shelves do not take up the entire space, instead, they are separated within an aisle-like space that acts as a conduit. People crossing the corridors can be compared with specific patterns as they shop for protein molecules that move somewhat randomly within the nucleus channels according to Brownian rules of motion. No matter how congested the lane is, people always find a way to pass each other, while maintaining some distance as they go. Molecules crossing the molecular channels do the same without any traffic issues on their way. This allows each molecule to travel efficiently, maintaining supermarket regularity.
The effect of viscosity
Molecules in eukaryotic cells have different sizes. For example, ions are subnanometer in size, and protein radii are usually few nanometers; The radius of the nuclear particle is about 5.5 nm, while the radius of the folded chromatin fibers is about 15 nm. Moreover, condensed chromatin rings form higher level compact structures characterized by a radius of about 150 nm. To understand its ability to move within the nucleus, Professor Ho? Yst development of nanometer-sized objects that cover the entire spectrum of natural components – the length scales found in the nucleus. Polymers, proteins, and nanoparticles with radii from 1.3 to 86 nm were considered.
To see this interesting organization at the nanoscale level, the transport of specific molecules has been studied using non-invasive techniques such as fluorescence correlation spectroscopy (FCS) and bitmap correlation spectroscopy (RICS). Thanks to materials such as GFP (green fluorescent protein) or rhodamine-based nanoparticles in nanomolar concentration, it was possible to monitor the mobility of specific molecules and determine the viscosity of the nucleoplasm without causing any disturbance to cellular activity. These techniques allow scientists to investigate even the slightest changes at the molecular level. The motion of large nanoparticles is reduced by up to 6 times compared to diffusion in aqueous medium. However, the diffusion of typical molecules was reduced by protein size only 2-3 times. Mobility decreases dramatically when the radius of the injected objects is greater than 20, and is more important in estimates of the diffusion coefficient, and it is possible to look closely at the movement and interaction of particles that occur between specific organisms in the nucleus channels and within a packed structure within the nucleus. These measurements broaden our current understanding of the structure of the kernel. Having a good understanding of the intricacy of channels within the nuclei is crucial because it directly contributes to our knowledge of how large biotic structures, including near-future medicine, are transported within the cell.
The first author, Dr. Grzegorz Bubak notes, “Our experiments revealed that the nucleus of the eukaryotic cell infiltrates by 150 nm-wide interploid channels filled with a dilute aqueous protein solution of low viscosity.”
Studies that determine the size of crowding within the nuclei of cells reveal that most molecules can freely pass through this complex structure. Based on experiments supported by theoretical models, it was possible to estimate the width of channels (~ 150 nm) between the chromatin architecture. The cores’ channels can make up to 34% of the nuclei volume which is around 240 μl. If they are narrower, the chromatin fibers will be more dispersed, making the efficient movement of the molecules within them impossible. It’s amazing that the nucleus can contain such large amounts of DNA and other chemical elements without disturbing the migration of molecules. All this thanks to the well-ordered chromatin fibers made of DNA with the structural proteins that give the double helix its shape. The transport of certain chemical elements through the biological fluid in molecular channels is essential in many processes, such as the creation of specific molecules and the formation of new complex protein structures.
“These results could be of great interest when designing biological drugs such as therapeutic proteins, enzymes, and monoclonal antibodies, which can have greater hydrodynamic radii than conventional synthetic chemical drugs.” – Dr. concluded. Popcorn
As a result of these studies, the mobility of particles in nuclear channels is now being described in detail and well understood for the first time. Thanks to the research presented in this work, we now know how chromatin fibers control the regulation of molecules, revealing an interesting molecular mechanism hidden deep in the nucleus. We are now one step closer to developing therapeutic agents that can be effectively transferred to the nucleus.