'Cellular glue' may help us finally build tissues and organs
Researchers from the University of California, San Francisco, (UCSF) engineered molecules that function as “cellular glue,” enabling them to precisely direct how cells bond with each other. This is a significant step toward regenerative medicine's long-term goal of creating new tissues and organs, according to a press release.
Adhesive molecules are naturally present in the body and keep the tens of trillions of cells together in organized patterns. They build neural networks, develop structures, and direct immune cells to specific areas of the body. Adhesion also makes cell communication easier to maintain the body functioning as a self-regulating whole,
“We were able to engineer cells in a manner that allows us to control which cells they interact with, and also to control the nature of that interaction,“ said Wendell Lim, Ph.D., the Byers Distinguished Professor of Cellular and Molecular Pharmacology and director of UCSF’s Cell Design Institute. “This opens the door to building novel structures like tissues and organs.
Engineering new adult cells to make new connections
Body organs and tissues form in utero and continue to develop throughout childhood. Many of the molecular instructions that control these generative processes have vanished by adulthood, and some tissues, like nerves, are incapable of recovering from injury or disease.
Lim aims to overcome this by engineering new adult cells to make new connections. However, this requires an ability to engineer how cells interact with one another.
“The properties of a tissue, like your skin, for example, are determined in large part by how the different cells are organized within it,” said Adam Stevens, Ph.D., the Hartz Fellow in the Cell Design Institute and the first author of the paper. “We’re devising ways to control this organization of cells, which is central to being able to synthesize tissues with the properties we want them to have.”
How firmly a tissue's cells are bound together contributes significantly to its distinctness. Many of the cells will be very tightly bonded in solid organs like the liver or lungs. In the immune system, however, weaker bonds allow the cells to pass through blood arteries or crawl between the tightly bound cells of skin or organ tissues in order to reach a pathogen or a lesion.
The researchers designed their adhesion molecules in two parts to control the quality of cell bonding. One part of the molecule functions as a receptor outside of the cell and chooses which other cells it will contact with. The strength of a bond is tuned by a second component located inside the cell. The two parts are interchangeable in a modular method to produce a variety of specialized cells that bond in various ways across a range of cell types.
Revealing "a flexible molecular adhesion code"
According to Stevens, these discoveries may also work for additional applications. To make it simpler to investigate illness states in human tissue, researchers may, for instance, create tissues to model disease states.
Custom adhesion molecules may provide a fuller knowledge of how the transition from single to multicellular species occurred. Cell adhesion was a crucial milestone in the evolution of mammals and other multicellular organisms.
“It’s very exciting that we now understand much more about how evolution may have started building bodies,” he said. “Our work reveals a flexible molecular adhesion code that determines which cells will interact, and in what way. Now that we are starting to understand it, we can harness this code to direct how cells assemble into tissues and organs. These tools could be really transformative.”
The results of the study were published in Nature on December 12, 2022.
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