Researchers at the University of California San Francisco (UCSF) have designed molecules that act as “cell glue“, allowing them to precisely direct the way cells stick to each other. The discovery represents an important step towards the construction of tissues and organs, a long-awaited goal of regenerative medicine.
Adhesive molecules are found naturally throughout the body, holding its tens of trillions of cells together in highly organized patterns. They form structures, create neural circuits, and guide immune cells to their targets. Adhesion also facilitates communication between cells so that the organism continues to function as a self-regulating whole..
In a new study, published in the journal Nature, researchers created cells with personalized adhesion molecules that bind to specific partner cells in a predictable way to form complex multicellular assemblies.
«We were able to design cells in a way that allows us to control which cells they interact with, and also control the nature of that interaction.says lead author Wendell Lim, of the UCSF Institute for Cellular Design. “This opens the door to building novel structures like tissues and organs.”
Body tissues and organs begin to form in the womb and continue to develop throughout childhood. By adulthood, many of the molecular instructions that guide these generative processes have disappeared, and some tissues, such as nerves, cannot heal from injury or disease.
Lim hopes to overcome this situation by designing adult cells that make new connections. But for this, one must know how to design precisely how cells interact with each other.
«The properties of a tissue, such as skin, for example, are largely determined by how the different cells that make it up are organized», explains Adam Stevens of the Institute for Cellular Design and first author of the article.
“We are devising ways to control this organization of cells, which is critical to being able to synthesize tissues with the properties we want them to have.”
Much of what distinguishes a given tissue is how tightly packed its cells are. In a solid organ, such as a lung or liver, many of the cells will be held together quite tightly. But in the immune system, weaker links allow cells to flow through blood vessels or crawl between tightly bound cells in skin or organ tissue to reach a pathogen or wound.
Tissues could be designed to model disease states and facilitate their study in human tissues
To drive that quality of cell attachment, the researchers designed their adhesion molecules in two parts. One part of the molecule acts as a receptor on the outside of the cell, determining which other cells it will interact with. A second part, inside the cell, tunes the strength of the union that is formed. The two parts can be mixed and matched in a modular fashion, creating a set of custom cells that come together in different ways across the spectrum of cell types.
According to Stevens, these discoveries have other applications as well. For example, researchers could design tissues to model disease states and facilitate their study in human tissues.
Cell adhesion was a key event in the evolution of animals and other multicellular organisms, and personalized adhesion molecules could offer a deeper understanding of how the journey from unicellular to multicellular organisms began.
«It’s very exciting that we now understand so much more about how evolution may have started to build organisms.», he assures. ‘Our work reveals a flexible molecular adhesion code that determines which cells will interact and in what way. Now that we begin to understand it, we can harness this code to direct the way cells assemble into tissues and organs. These tools could be truly transformative.”