DNA engineered to mimic biological catch bonds

Dr. Isaac Li and his team in the Irving K. Barber College of Science study biophysics at the single-molecule and single-cell levels. Their research focuses on understanding how cells physically interact with each other and their environment, with the ultimate goal of developing innovative tools for disease diagnosis and treatment.

Two of Dr. Li’s doctoral students, Micah Yang and David Bakker, designed a new molecule that changes the way cells adhere to and communicate with each other.

Micah Yang, the study’s lead author, explains that all cells have a natural “stickiness” that allows them to communicate, stick together, and form tissues. Unlike everyday glues, which release more easily with increased force, many cell-adhesive interactions behave in the opposite direction—the harder you pull, the stronger their stickiness becomes. This counterintuitive, self-reinforcing stickiness, known as a “catching key,” is essential for facilitating basic biological functions and maintaining integrity.

Yang’s innovation involves a pair of DNA molecules designed to replicate this trapping bond behavior.

Dubbed the “fishhook” for its unique structure, this DNA-based system consists of two parts: a fish and a fishhook. Utilizing complementary DNA base pair interactions, the system functions like a fish biting a hook, forming a capture bond. By modifying the DNA sequences of the fish and the hook, the behavior of this bond can be precisely fine-tuned, allowing its strength to be controlled under different forces.

“Capture bonds play key roles in systems such as T-cell receptors and bacterial adhesion, which are key to immune responses, tissue integrity and mechanosensing (the ability of cells to detect and respond to physical forces),” Yang said. “Nature has perfected these interactions over millions of years, but until now synthetically replicating their dynamics has been a major challenge.

The research was recently published in nature communicationshighlighting the advantages of this novel DNA-based system.

“The system’s adjustability is a significant improvement over previous manual capture bonds,” Yang said. “The ability to precisely control the force-dependent behavior of bonds makes it an ideal tool for studying biological interactions and developing innovative materials.”

Yang said the potential applications for fishhook bonding are vast.

In materials science, the design could inspire the creation of responsive materials that become stronger under stress, making them ideal for wearable technology or aerospace applications where durability is critical.

In medicine, this approach could improve drug delivery systems or tissue scaffolds so that they can interact with cells in a force-sensitive manner, mimicking natural biological processes.

While the development of artificial bonding is still in its early stages, Young sees it as an exciting step in biomimetic engineering – a method that seeks to replicate the efficiency and adaptability of natural systems. This work opens up new possibilities for designing materials that mimic or enhance natural biological processes.

“By mimicking biological interactions such as capturing bonds, scientists not only learn more about how these systems work in nature, but also pave the way for new technologies that can improve human life.”