Ligand-Receptor Interactions and Cellular Adhesion

The dynamics of molecular interactions dictate many important cellular adhesion events. For instance, during the human immune response to infection, patrolling cells in the blood and lymph migrate through tissue through repetitive attachment-detachment sequences as they inspect potential targets. Similarly, metastasis, or cancer spreading, relies on site-specific recognition that is moderated by “molecular handshakes” between adjacent cells. Clarifying the cooperativity between a ligand-receptor pair’s range of attraction and the time required for them to bind is crucial for understanding these adhesion mechanisms and for designing biomimetic adhesive materials.

Using Mother Nature as a template, we create model membranes to directly measure the adhesion between membranes as a function of ligand-receptor bond strength, density of receptors, contact mechanics and dynamics. We then fold this fundamental physical understanding into simulations to obtain predictive abilities for rationally engineering biomimetic surfaces and liposomal-based, targeted drug delivery systems.

Model architectures are evaluated using the Surface Forces Apparatus (SFA), which mounts the surfaces on opposing mica substrates. Curved for handling, the SFA can maneuver the surfaces with near-angstrom precision for accurate measurement of distance and force (±50pN).