Structure formation in mini-organs

Bird’s-eye view of an organoid of the human mammary gland with numerous branches that end in spherical alveoli. Credit: Benedikt Buchmann

The development of alveoli in organoids derived from mammary gland tissue follows the same physical principles as the formation of discrete droplets in a stream of water.

Many organ systems found in animals exhibit very complex structures, which are essential for their various functions. How such structures develop during embryonic development is a central question in biology. Physicists led by Erwin Frey (professor of statistical and biological physics at LMU Munich) and Andreas Bausch (professor of cell biophysics at Technical University of Munich) studied this fundamental problem using mini-organs called organoids as an experimental system. The team focused on the spherical “alveoli” in which the ducts of the lactating mammary gland terminate. The study demonstrated in detail that these alveoli form according to the same principles as droplets in a jet of water coming out of a pipe.

The experimental work was performed in Bausch’s lab and used mammary gland organoids grown in culture from excised human tissue. Organoids are three-dimensional model systems that exhibit many physiologically relevant properties of the organ from which they originate. Thus, the organoids of the mammary gland form ducts that branch out into groups of smaller tubular structures, each terminating in a spherical sac or alveolus. This architecture is typical of the lactating human mammary gland, but it is also found in many other organs including the lung. Bausch and his group were able for the first time to follow the growth dynamics of mini-organs over several days by time-lapse microscopy. In addition, they investigated the micromechanical response of developing tissue to localized laser-induced cell ablation.

Using this strategy, the researchers were able to link the formation of spherical alveoli to a change in the direction of cell movement in developing tissue. The cells in each tubule are constantly in motion, pulling on their immediate neighbors. At first, they collectively migrate back and forth along the walls of the tubules. “But at some point, the cells at the end of the tubules begin to follow a rotational path. This change in behavior, along with interactions between neighboring cells, then spreads back and forth until all cells close to the end of a branch begins to turn. as a collective, “says Andriy Goychuk, member of Erwin Frey’s research group and co-first author of the publication. His colleagues Pablo Fernandez and Benedikt Buchmann of the group of Andreas Bausch, who carried out the ablation experiments, explains what happens as follows: “The alveoli no longer exert the same force in all directions, which results in an alteration of their trajectories. which alternate forward and backward movement exert more force in the direction of the axis of the tube than around its circumference, is no longer the case for cells that follow a rotational stroke. prominent along the circumference, the tip of each tube develops into a spherical protrusion. “

According to the authors, the mode of formation of spherical protuberances is analogous to the mechanism responsible for the formation of drops in a water jet. Like the cells of the developing organoid, the surface of the water jet is under tension. All objects subjected to a tensile force try to minimize their surface. Since the area of ​​a sphere is smaller than that of a cylinder, the water jet breaks up into discrete droplets and in the tissue of the mammary gland, the rotation of the main cells changes the balance of forces in the tubular branches in such a way that they become unstable, as in the case of the water jet, and form spherical protuberances. “This theoretical model provides an important framework for the analysis of more complex geometric transformations in biological tissues, such as those that occur during the development of the salivary glands, pancreas, kidney and lung,” explains Frey.

Mechanical stimuli significantly influence organ growth

More information:
Erwin Frey et al, Surface tension induced budding induces alveologenesis in organoids of the human mammary gland. Nat. Phys. 17, 1130-1136 (2021).

Provided by Ludwig Maximilian University Munich

Quote: Structure formation in mini-organs (2021, 5 October) retrieved on 5 October 2021 from

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