Cellular Adhesive Regenerates Nerves

Cellular Adhesive Engineered to Regenerate Nerves Researchers at UC San Francisco (UCSF) have designed molecules that act like "cellular adhesive" and enable precise direction of how cells bind to one another. This design represents a major step toward tissue and organ construction, a long-targeted goal of regenerative medicine. Adhesive molecules occur naturally in the body and hold tens of trillions of cells together in highly organized patterns. These molecules build structures, form neural circuits, and direct immune cells to their targets. Adhesion also facilitates communication between cells to enable the body to function as a self-organizing whole. In a new study published in the 12 December 2022 issue of Nature, researchers engineered cells containing specialized adhesion molecules that bind in predictable ways to specific partner cells to create complex multicellular assemblies. Wendell Lim, senior author and Director of the Cell Design Institute at UCSF and Professor of Cellular and Molecular Pharmacology, stated: "We were able to design cells such that we could control which cells they interact with and at the same time control the nature of that interaction. This opens the door to building new structures like tissues and organs." Renewing Connections Between Cells Body tissues and organs begin to form in the womb and continue to develop through childhood. By adulthood, the molecules that guided these productive processes have disappeared, and some tissues like nerves cannot resist injury and disease. Lim hopes to overcome this by engineering adult cells to form new connections. But doing so requires the ability to precisely engineer how cells interact with one another. PhD Adam Stevens, Hartz Fellow at the Cell Design Institute and first author of the paper, said: "The properties of a tissue, such as our skin, are determined in large part by how different cells are organized within it. We are developing ways to control this cell organization, which is at the heart of our ability to synthesize tissues with the properties we want them to have." Much of what distinguishes one tissue from another is how tightly its cells are bound to each other. In a solid organ like the lung or liver, most cells bind quite tightly. But in the immune system, weaker bonds allow cells to escape from blood vessels or creep between tightly bound cells of skin or organ tissue to reach a pathogen or wound. To direct this cell-binding quality, researchers designed adhesion molecules in two parts. One part of the molecule serves as a receptor outside the cell and determines which other cells it will interact with. A second part inside the cell adjusts the strength of the resulting bond. The two parts can be mixed and matched in a modular fashion, creating a set of specialized cells that bind differently across a spectrum of cell types.

The Code Underlying Cellular Assembly

Stevens said these discoveries have other applications as well. For example, researchers could design tissues to model disease states to facilitate work in human tissue. Cell adhesion was an important development in the evolution of animals and other multicellular organisms. Specialized adhesion molecules can provide deeper understanding of how the path from single-celled to multicellular organisms began. Stevens concluded: "It is very exciting that we now understand much more about how evolution might have begun to build bodies. Our work reveals a flexible molecular adhesion code that determines how cells interact with one another in particular ways. Now that we are beginning to understand it, we can use this code to direct how cells come together into tissues and organs. These tools are truly transformative." Academic reference: Adam J. Stevens, Andrew R. Harris, Josiah Gerdts, Ki H. Kim, Coralie Trentesaux, Jonathan T. Ramirez, Wesley L. McKeithan, Faranak Fattahi, Ophir D. Klein, Daniel A. Fletcher, Wendell A. Lim. Programming Multicellular Assembly with Synthetic Cell Adhesion Molecules. Nature, 2022; DOI: 10.1038/s41586-022-05622-z Source: https://www.sciencedaily.com/releases/2022/12/221212140159.htm