Adhesion from tethered ligand-receptor bonds with microsecond lifetimes

It was already known that biological ligand-receptor interactions often involve bonds with short lifetimes. Classical thermodynamic models suggest that many of these bonds last less than 2 milliseconds. Some of these bonds exist for only nanoseconds to microseconds. Despite their brief existence, these bonds are essential for cellular adhesion and signaling. However, the mechanical forces they can withstand remain poorly characterized. This uncertainty drove the need for a method to quantify the adhesion from such transient interactions. Prior research has shown that multiple weak bonds can collectively contribute to strong adhesion. But the exact contribution of individual short-lived bonds is unclear. This gap motivated the development of a new experimental approach to measure these forces directly.

The aim of this study was to quantify the forces and adhesion provided by ligand-receptor bonds with microsecond lifetimes. The researchers focused on bonds that are too short-lived to be measured using conventional techniques. They sought to understand how these bonds contribute to overall adhesion between surfaces. The study used a model system with known bond properties to simulate biological interactions. The goal was to measure the forces required to rupture these bonds and the resulting adhesion. The researchers also aimed to determine how many bonds remain bound simultaneously. They wanted to explore whether the cumulative effect of many weak bonds could mimic the strength of a single strong bond. This work aimed to provide insights into how transient bonds function in biological systems.

The researchers used an automated surface forces apparatus to measure interactions between two model surfaces. One surface was coated with streptavidin receptors, and the other had flexible PEG tethers. Each tether anchored a weakly binding ligand called HABA. The surfaces were brought into contact to form multiple ligand-receptor bonds. The apparatus measured the forces required to separate the surfaces. The experiment simulated the adhesion between cellular membranes. The researchers tracked the number of bonds that remained bound during the interaction. They also recorded the lifetime of individual bonds using high-resolution measurements. The setup allowed them to study the cumulative effect of many weak bonds. This approach mimicked the natural strategy of using multiple transient interactions for adhesion.

The study found that the HABA-streptavidin bond had a median lifetime of less than 100 microseconds. The forces required to rupture these bonds were relatively low, consistent with their weak binding. Only a small fraction of the available bonds remained bound at any given time. The bond energy was measured at approximately 10.5 kBT, close to the average observed in natural systems. The researchers observed that the bonds frequently dissociated and reformed during the interaction. The cumulative adhesion from multiple bonds was significant despite the short lifetime of each. The results showed that the strength of the overall adhesion increased with the number of bonds. These findings support the idea that transient bonds can collectively provide strong adhesion.

The authors suggest that the cumulative effect of many weak bonds can produce strong adhesion between surfaces. They propose that the low forces required to rupture these bonds are consistent with their short lifetimes. The study supports the idea that transient bonds can contribute to cellular adhesion and signaling. The researchers emphasize that the bond energy of HABA-streptavidin is similar to that of natural ligand-receptor interactions. They argue that the frequent dissociation and reformation of bonds may be a common feature of biological adhesion. The results exemplify how nature uses multiple weak bonds to achieve functional adhesion. The authors suggest that this mechanism may be important for processes like cell migration and immune responses. They conclude that the strength of adhesion depends on the number of bonds rather than the strength of individual bonds.