The research conducted at UC Santa Barbara and the Physics of Life Excellence Cluster of TU Dresden has uncovered a fascinating discovery. Biophysicist Otger Campàs and his team have demonstrated that cell nuclei wield significant control over the architecture and mechanics of eye and brain tissues during embryonic development.
These findings expand our understanding of the cell’s nucleus, revealing its far-reaching influence on tissue organization in addition to its established role in genetic regulation.
“We were measuring tissue stiffness in the zebrafish retina and realized that it depended on the packing of nuclei. This was totally unexpected because tissue mechanics is believed to depend on cell surface interactions, but not organelles inside cells,” said Campàs, now professor and the chair of tissue dynamics at the Cluster of Excellence Physics of Life at TU Dresden, where he also serves as managing director.
The intricate functions of organelles within cells are crucial for the development of tissues and organs. Just like the vital roles of factories and roads in cities, organelles perform essential tasks within cells, enabling them to function effectively. Although it was previously believed that organelles confined within cells did not directly contribute to organ development, recent findings challenge this notion.
Among the organelles, the nucleus is recognized for its role in information processing within cells, controlling gene expression in response to signals. However, the nucleus, being the largest and stiffest organelle, might also impact the physical structure of tissues. This realization led Campàs to investigate the influence of nuclei on organ formation.
Furthermore, prior research by Campàs’s group demonstrated that cell collectives behave like a foam during development, allowing tissues to either solidify or flow and change shape. These insights shed light on the significant role of organelles, particularly the nucleus, in shaping the formation of organs.
“By extending the Active Foam Model, we identified a new mode of solid-to-fluid transition, governed by the relative nucleus and cell sizes,” said co-lead author Sangwoo Kim.
In their research, the authors discovered that the size of the nucleus relative to the cell in eye and brain tissues, both in experimental and theoretical scenarios, directly influenced tissue stiffness when the nucleus occupied a significant portion of the cell space. Additionally, they observed that densely packed nuclei resulted in the cells arranging themselves into nearly crystalline structures.
“When the nuclei start to interact mechanically, both tissue mechanics and cellular ordering are not dictated by the cell surface, but rather controlled by the nucleus itself,” Campàs said. “This is an organelle determining the stiffness of the entire tissue.”
The findings of their research call into question the established beliefs, uncovering a fresh role for nuclei in governing tissue structure and mechanics.
In their investigation of the impact of cell nucleus size on organ development, the scientists utilized zebrafish. These organisms serve as a valuable model for studying developmental processes due to their transparency during embryonic stages and rapid maturation, enabling the visualization of 3D organ formation.
“We therefore conducted structural measurements and cell movement quantifications, focusing on the developing retina and brain of zebrafish,” said co-lead author Rana Amini.
The authors’ measurements illustrated that changes in cell and nuclear sizes during crucial developmental stages tightly pack the nuclei, like coffee beans in a jar. This organized structure is vital for the eye’s functionality, as the orderly packing of cells is essential for processing visual cues. In zebrafish, the jamming of nuclei during eye development also results in a crystalline order of cells.
In addition to the eye, the team discovered that brain tissues also experience nuclear jamming, indicating a new role for the nucleus in shaping neural tissue architecture. This finding suggests that defects at the nuclear level could lead to diseases linked to impaired tissue structure. This new insight brings us closer to understanding how cells construct organs during embryonic development.
Journal reference:
- Sangwoo Kim, Rana Amini, Shuo-Ting Yen, Petr Pospíšil, Arthur Boutillon, Ilker Ali Deniz & Otger Campàs. A nuclear jamming transition in vertebrate organogenesis. Nature Materials, 2024; DOI: 10.1038/s41563-024-01972-3