Molecular "glue" to repair injuries, restore neurons, regenerate tissues

Health News -- December 14, 2022: Scientists at UC San Francisco (UCSF) have created molecules that function
as "cellular glue," enabling them to precisely

control how cells adhere to one another. The discovery is a significant step toward regenerative medicine's long-term
goal of creating new tissues and organs.

The body naturally contains adhesive molecules that hold the tens of trillions of cells together in intricate patterns.
They build neural circuits, shape structures, and direct immune cells toward their intended targets. In order to maintain
the body's ability to function as a self-regulating whole, adhesion also makes cell communication easier.

In a recent study, tailored adhesion molecules were designed into cells that joined with specified partner cells in predictable ways to build complex multicellular ensembles. The findings were published in the edition of Nature on December 12, 2022.

"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 senior author Wendell Lim, PhD, 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."

Cell-Cell Communication Regeneration

Body organs and tissues start to grow in pregnancy and continue to do so throughout life. Many of the molecular instructions that control these generative processes by adulthood have vanished, and some tissues, like nerves, are incapable of recovering from damage or illness.

By creating new connections between adult cells, Lim aims to overcome this. However, to achieve this, one must be able to precisely engineer how cells communicate with one another.

The degree to which a tissue's cells are joined together determines how distinctive it is in large part. Many of the cells of a solid organ, such as the liver or lungs, will be very closely connected. The immune system, however, uses weaker connections to allow cells to go through blood vessels or squeeze between the tightly packed cells of skin or organ tissues in order to access a pathogen or a lesion.

The researchers divided the design of their adhesion molecules into two portions to control that aspect of cell interaction. On the outside of the cell, a portion of the molecule functions as a receptor and chooses which other cells it will contact with. The strength of the bond that formed is tuned by a second component located inside the cell. The two components are interchangeable in a modular method to produce a variety of specialized cells that bind in various ways across a range of cell types.

The Coding That Supports Cellular Assembly

According to Stevens, these discoveries also have other uses. To make it simpler to investigate illness states in human tissue, researchers could, for instance, create tissues that imitate disease states.

Custom adhesion molecules may provide a fuller knowledge of how the transition from single to multicellular species began. Cell adhesion was a crucial milestone in the evolution of mammals and other multicellular organisms.

"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, PhD, 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."

Josiah Gerdts, Ki Kim, Wesley McKeithan, Jonathan Ramirez, Faranak Fattahi, Coralie Tentesaux, Ophir Klein, and Andrew Harris are additional authors from the UCSF Cell Design Institute, Department of Cellular and Molecular Pharmacology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Cellular and Molecular Pharmacology, and Department of Orofacial Sciences.

University of California, San Francisco, is the source of the information. "Cellular "glue" to repair injuries, restore nerves, and regenerate tissues." ScienceDaily. www.sciencedaily.com/releases/2022/12/221212140159.htm, ScienceDaily, 12 December 2022.

WNCTIMES by Marjorie Farrington