Recent research breakthroughs from Scripps Research have shed light on the fascinating connections among a primordial inorganic polymer known as polyphosphate (polyP), magnesium ions, and DNA.
This interdisciplinary investigation provides new perspectives on cellular mechanisms, hinting at innovative strategies for drug development.
Key Findings on DNA and Polyphosphate
Published in *Nature Communications*, this study identifies a “Goldilocks” zone—the perfect range of magnesium concentration necessary for DNA to coil around polyP-magnesium ion condensates.
This interaction leads to the creation of microscopic droplets with liquid-like properties, which could significantly improve how genetic material is organized and protected within cells.
The research was led by Associate Professor Lisa Racki and Professor Ashok Deniz from the Department of Integrative Structural and Computational Biology at Scripps Research.
Racki was already studying these structures in bacterial systems, while Deniz was delving into the physical chemistry of biomolecular condensates.
Their combined expertise played a crucial role in unlocking these ancient biochemical relationships.
Observations on DNA Shells and Condensates
Racki was taken aback when she discovered that globular forms of DNA were interwoven with these condensates, even though she was already aware of their close proximity in cellular environments.
Deniz added that observing the behavior of DNA shells and how they might affect polyP condensates sparked intriguing scientific questions.
Utilizing advanced microscopy techniques, the team illustrated how DNA spirals around these condensates, forming a protective layer similar to an eggshell.
This unique structure not only affects molecular movement but also influences how the condensates behave dynamically, particularly during their merging process.
When the DNA shell is absent, the condensates tend to merge uncontrollably, much like when oil and vinegar mix in salad dressing.
A closer examination showed that the rate of merging varied with the length of the DNA strands involved.
Longer DNA strands likely created more intricate entanglements on the surfaces of the condensates, reminiscent of the tangling observed with longer hair compared to shorter hair.
Implications for Drug Development
Since DNA is over 1,000 times thinner than the condensates, visualizing these interactions posed significant challenges.
To tackle this, the researchers collaborated with Assistant Professor Danielle Grotjahn and Scripps Fellow Donghyun Raphael Park, utilizing cryo-electron tomography.
This groundbreaking imaging method, which relies on electrons instead of light, enabled the team to capture high-resolution, three-dimensional images of quickly frozen samples, revealing DNA filaments extending from the condensates, akin to tangled hair.
Another pivotal finding was the identification of a specific magnesium concentration range that facilitates the formation of DNA shells.
Outside of this range, these shells fail to form, highlighting the remarkable precision with which cellular systems can regulate the characteristics of condensates.
Racki emphasized that cellular interfaces—often perceived simply as boundaries—can play a role in reconfiguring molecular landscapes.
Rather than resulting in chaotic tangles at the condensate boundaries, these interfaces foster structured interactions.
Continuing this line of inquiry may lead to insights into DNA supercoiling, a process similar to a spring’s twisting that allows for efficient DNA packing in cells.
Racki mentioned that phenomena associated with DNA supercoiling could have remote effects, suggesting that changes in one section of DNA might impact other distant regions.
The researchers are optimistic that their studies will help clarify how local modifications in DNA structures can influence gene expression and overall cellular functioning.
Looking forward, they are excited about the potential to apply these findings toward easier and more effective methods for cellular manipulation and drug development in biomedical contexts.
Source: ScienceDaily