Research conducted at UC Santa Barbara and the Physics of Life Excellence Cluster at TU Dresden by biophysicist Otger Campà s and his team has revealed that cell nuclei play a crucial role in shaping the structure and mechanics of eye and brain tissues during the development of embryos. These findings introduce an additional function of the cell’s nucleus in organizing tissues, surpassing its well-known role in regulating genes.
“While we were analyzing the stiffness of the zebrafish retina, we discovered that it was influenced by how the nuclei were arranged. This was surprising, as it was previously thought that the mechanics of tissues depended solely on interactions at the cell’s surface rather than on the organelles inside,” explained Campà s, who is currently a professor and head of tissue dynamics at the Cluster of Excellence Physics of Life in TU Dresden, where he also serves as the managing director. This research, which has been published in Nature Materials, opens up new avenues to comprehend how cells manage embryonic development.
The Hidden Architect
Each cell contains structures called organelles that carry out essential functions, yet how these organelles contribute to tissue and organ formation remains unclear. Much like factories or infrastructure in a city, numerous organelles execute various tasks within cells to ensure their proper operation. Since organelles are contained within cells, it was generally believed that they did not directly influence organ development during the early stages of life. That belief has now been challenged.
The nucleus is an organelle primarily known for managing information in cells, controlling gene activation in response to incoming signals. However, it is also the largest and most rigid organelle, potentially impacting the physical structure of tissues in addition to its informational roles. Intrigued by the nucleus’s possible influence on tissue formation, Campàs decided to examine the role of nuclei in organ development.
Previous innovative studies by his team had shown that groups of cells behave similarly to foam during development, capable of either ‘jamming’ to stabilize tissue structure and shape or ‘melting’ to allow tissues to flow and be reshaped.
“By applying the Active Foam Model, we discovered a new mechanism for the solid-to-fluid transition, which is influenced by the relative sizes of nuclei and cells,” said co-lead author Sangwoo Kim.
When the researchers compared the size of nuclei to that of cells in the eye and brain tissues through both experimental and theoretical approaches, they found that when the nucleus occupied a significant portion of the cell, it directly governed the tissue’s stiffness. They also observed that closely packed nuclei organized the surrounding cells into nearly crystalline formations.
“As nuclei begin to interact mechanically, it turns out that both the mechanics of the tissue and the organization of cells are governed not by the cell surface but by the nucleus itself,” said Campà s. “This suggests that an organelle is in charge of the stiffness of the whole tissue.” Their study challenges long-held beliefs, revealing a new function for nuclei in the management of tissue structure and mechanics.
To investigate how nucleus size influences organ formation, the team used zebrafish, known for being valuable in developmental studies due to their transparency during the early stages of life and rapid maturation, facilitating the observation of organ formation in three dimensions.
“We conducted structural assessments and quantified cell movements, focusing particularly on the developing retina and brain of zebrafish,” stated co-lead author Rana Amini.
Through these assessments, the researchers showed that changes in the sizes of cells and nuclei during critical stages of development cause nuclei to be compactly arranged as they become closely enveloped by neighboring cells. In this process, nuclei fit together snugly, similar to coffee beans in a container, which could be crucial for the proper functioning of the eye. In both our eyes and those of zebrafish, the organization of cells appears highly structured, often exhibiting a regular, “crystalline” arrangement essential for processing visual information. The crystalline structure observed in zebrafish cells seems to result from the jamming of nuclei throughout eye development.
The findings extend beyond the eye, demonstrating that brain tissues also experience nuclear jamming, thus unveiling a new function for the nucleus in directing the structure of various neural tissues. This research further suggests that abnormalities at the nuclear level may contribute to diseases linked with disrupted tissue architecture. Each new insight brings us closer to understanding the mechanisms by which cells construct organs during embryonic development.
