Abstract

In the human body, a vast variety of different molecules is circulating, diffusing, and interacting. Cell membranes contain many proteins that are responsible for interacting and communicating with their environment. Some examples are adhesion molecules for cell anchorage or locomotion, membrane pores for molecular exchange, and other receptor molecules. The receptor molecules specifically screen for information mediated by ligand-molecules (e.g., hormones) that match the binding site. Some cellular receptor molecules act like “noses,” programmed to transduce the event of a bound ligand through the membrane into the cell by a conformational change (e.g., G-protein-coupled receptors). A change in conformation is a synonym for a mechanical deformation of the molecule. This often triggers a molecular reaction inside the cell by a signaling cascade. A few ligand molecules (e.g., chemokines) might change the behavior of the whole cell, for example, the directed motion along a concentration gradient. For cellular motion, reversible adhesion and force are required. In order to react adequately to external stimuli, a cell can utilize different concepts for tuning its adhesion by directly strengthening the adhesion of an adhesion molecule (affinity), by increasing the number of available adhesion molecules (avidity), or by altering the properties of the cellular anchor of the adhesion molecule. Additionally, the cell can distribute an external load to its adhesion molecules either in a sequential manner (pealing offfrom the adhesion site one bond after the other at low forces) or in parallel to the grouped adhesion molecules (clustered weak bonds that share the load in parallel and add it up to a very high force). To resolve the concepts behind cellular adhesion, techniques with a single molecular resolution as well as techniques that reveal multi-molecular arrangements are required. Force spectroscopy is a technique that measures forces within or between individual molecules. Performing such experiments on living cells at the level of single molecules not only reveals the strength of a molecular bond but also adhesion strategies and mechanical reactions of cells related to external forces. Like the receptor molecules, the adhesion molecules also scrutinize their environment for specific ligands, but they rather aim at mediating motility or anchorage of the cell. Some adhesion molecules also change their conformation if a ligand has bound and trigger molecular reactions inside the cell. With this concept, the cell can sense the mechanical and chemical properties of the environment it adheres to and consequently react to it. In the following chapter, the technique of force spectroscopy is applied to address questions about cell adhesion forces. How strong is the cell’s adherence? What is the maximum force with which a cell can adhere? How does the cell regulate the adhesion strength? What force binds a single adhesion molecule to its ligand?