KANAZAWA, Japan, April 3, 2025 /PRNewswire/ -- Researchers at Nano Life Science Institute (WPI-NanoLSI), Kanazawa University and colleagues have achieved a breakthrough in understanding sperm DNA packaging. Using high-speed atomic force microscopy (HS-AFM), they captured the real-time process of protamine (PRM)-induced DNA condensation, providing critical insights into fertility, genome stability, and future applications in medicine. Their findings are published in Nucleic Acids Research.

Why This Discovery is Important

In most cells, DNA is wrapped around proteins called histones, allowing it to be loosely packed and accessible for gene activity. However, in sperm cells, histones are replaced by protamines, which enable extreme DNA condensation. This compaction is essential for protecting genetic material during fertilization, ensuring efficient transport of DNA to the egg, and contributing to fertility and embryo development. Despite its importance, the precise steps of how protamines condense DNA into highly stable structures have remained unclear. Previous imaging methods could only capture static snapshots, leaving many questions unanswered. Now, for the first time, Richard W. Wong at Nano Life Science Institute (WPI-NanoLSI), Kanazawa University and collaborators have used real-time imaging to reveal the entire condensation process.

Key Findings

Using HS-AFM, the research team directly visualized the stepwise transformation of DNA structures as they bind to protamines. The study introduces a new CARD (Coil-Assembly-Rod-Doughnut) model, which describes the condensation process through four distinct stages: the Coil Stage, where DNA forms loose loops; the Assembly Stage, where protamines bind, increasing structural organization; the Rod Stage, where DNA becomes further compacted; and the Doughnut (Toroid) Stage, where the final stable structure forms. Additionally, researchers discovered that this packaging is reversible, meaning the structure can shift based on environmental conditions. These insights have major implications for understanding male infertility, chromatin biology, and gene therapy.

Potential Applications

Fertility research could benefit from insights into DNA packaging, helping to diagnose and treat male infertility. Gene therapy might improve through a better understanding of DNA compaction and its role in genetic material delivery in medical treatments. Synthetic biology and nanotechnology could also leverage these findings to develop new methods for manipulating DNA structures in biotechnological applications.

Expert Insights

"Our findings provide a dynamic view of how protamines shape sperm chromatin structure, a process essential for fertility and genome stability," says corresponding author Richard W. Wong. "This research not only enhances our understanding of reproduction but also has far-reaching implications for genetics and fertility treatments."

Glossary

Protamines (PRMs) are small proteins that replace histones in sperm cells, enabling DNA to be tightly packed.
Chromatin refers to the complex of DNA and proteins that form chromosomes; in sperm, it is highly condensed.
High-Speed Atomic Force Microscopy (HS-AFM) is an advanced imaging method that captures molecular changes in real time at the nanoscale.
DNA Condensation is the process by which DNA is compacted to become more stable. Toroid Structure is a ring-shaped DNA formation seen in sperm, which helps protect genetic material.

Figure 
https://nanolsi.kanazawa-u.ac.jp/wp/wp-content/uploads/thumbnail_c_2025_GoroNishide.jpeg

Caption: Conceptual representation of the spatiotemporal dynamics of protamine–DNA condensation, as elucidated by high-speed atomic force microscopy (HS-AFM). The DNA double helix integrated into the donut symbolizes the hierarchical chromatin compaction process observed in sperm, transitioning through coil, assembly, rod, and doughnut (CARD) stages. The careful handling reflects the molecular precision captured by HS-AFM, offering insights into protamine-driven genome packaging essential for sperm maturation and male fertility. This visualization underscores the interplay between chromatin architecture and reproductive biology at the nanoscale.

© Goro Nishide (2025)

Reference 
Goro Nishide, Keesiang Lim, Akiko Kobayashi, Yujia Qiu, Masaharu Hazawa, Toshio Ando, Yuki Okada, and Richard W. Wong, Spatiotemporal dynamics of protamine–DNA condensation revealed by high-speed atomic force microscopy, Nucleic Acids Research
DOI: 10.1093/nar/gkaf152
URL: https://doi.org/10.1093/nar/gkaf152

Funding and acknowledgements

We thank Prof. Noriyuki Kodera for providing the cationic lipid substrate, and we are grateful to all members of Richard Wong laboratory for their involvement. This work was supported by The World Premier International Research Center Initiative (WPI). This work was also supported by WISE Program for Nano-Precision Medicine, Science, and Technology of Kanazawa University by MEXT (to G.N), MEXT / JSPS KAKENHI grant number 24K18449 (to K.L.), 20H05939 (to Y.O.) and 22H05537, 22H02209, 23H04278 and 24H01276 (to R.W .W .) from MEXT Japan; and by JST CREST Grant Number JPMJCR22E3 (to R.W .W .), and by grants from the Hokuriku Bank grant (to K.L), the Takeda Science Foundation, Japan (to R.W .W .), and the Shimadzu Science Foundation, Japan (to R.W .W .).

Contact
Kimie Nishimura (Ms)
Project Planning and Outreach, NanoLSI Administration Office
Nano Life Science Institute, Kanazawa University
Email: nanolsi-office@adm.kanazawa-u.ac.jp

Kakuma-machi, Kanazawa 920-1192, Japan

About Nano Life Science Institute (WPI-NanoLSI), Kanazawa University

Understanding nanoscale mechanisms of life phenomena by exploring "uncharted nano-realms".

Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the nanoscale.

https://nanolsi.kanazawa-u.ac.jp/en/

About the World Premier International Research Center Initiative (WPI)

The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).

See the latest research news from the centers at the WPI News Portal: https://www.eurekalert.org/newsportal/WPI

Main WPI program site: www.jsps.go.jp/english/e-toplevel

About Kanazawa University

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.
http://www.kanazawa-u.ac.jp/en/

 

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