A Switch for Cell Adhesion

Max Planck scientists show that the adhesion of cell membranes strongly depends on the switching rates of adhesion molecules

The adhesion of cells is a fundamental process in immune defence and tissue development. Cell adhesion is mediated by adhesion molecules that are located on the cell surfaces. Cells can switch some of their adhesion molecules between active and inactive "conformational states". This switching process typically requires input of chemical energy, e.g. from ATP molecules. Researchers from the Max Planck Institute of Colloids and Interfaces in Potsdam, Germany have found a surprising resonance of switchable adhesion molecules in a theoretical model of cell membrane adhesion. The resonance effect depends on the characteristic switching times of the adhesion molecules and the elastic properties of the cell membranes, and may help to control cell adhesion (Physical Review Letters, 3 February 2006).

Cells adhere to other cells via adhesion molecules located on their surfaces. Each adhesion molecule on one cell binds to a "partner molecule" on the other cell. The two binding partners can be identical molecules, like two hands holding each other, or distinct molecules that fit together like a lock and key. Cadherins, for example, are adhesion molecules that often bind to identical cadherins, holding together cells of the same type in the development and maintenance of body tissues. Integrins and selectins, on the other hand, bind to distinct adhesion partners, for example during adhesion of white blood cells in an immune defence.

The adhesion of two cells involves a subtle balance between the attractive binding energies of the adhesion molecules and repulsive energies, which result from cell shape fluctuations or from large non-adhesive proteins that impede adhesion. In a healthy organism, cells have to control this balance between attraction and repulsion. For some cancers, mutations of adhesion molecules shift the balance and lead to abnormal cell-cell adhesion events and tumour growth.

Via gene expression, cells can regulate the numbers and types of adhesion molecules at their surfaces and, thus, the strength and specificity of their adhesiveness. But some cells are known to change their adhesiveness rather quickly, much more quickly than gene expression allows. These cells have adhesion molecules that can be switched between different states. Integrins, for example, are adhesion molecules that have at least two different conformational states. In a "stretched" conformational state, the integrins are active and can bind to their partners on an apposing cell surface. In a "bent" state, the integrins are inactive and cannot bind (see Fig. 1).

The numbers of active integrins are crucial for the adhesiveness of these cells. But besides mere numbers, other factors may count as well. Researchers from the Max Planck Institute of Colloids and Interfaces have recently shown that the characteristic switching times of adhesion molecules strongly affect the adhesiveness. The switching of an adhesion molecule between an active and an inactive conformation is a stochastic process, i.e. a process that occurs with a certain probability at a certain time. The conformational switching process can be characterized by the average switching times in the two directions (from active to inactive, and vice versa). The process typically requires the input of "chemical energy", e.g., from ATP molecules, at least in one direction.

The Max Planck scientists have theoretically studied the adhesion of membranes via switchable adhesion molecules. The two opposing forces in the adhesion balance of the membranes are the attractive forces of the adhesion molecules, and repulsive forces from membrane shape fluctuations. Both forces have characteristic times scales. These time scales are the switching times of the adhesion molecules, and the relaxation times of the membrane shape fluctuations. Interestingly, a resonance effect occurs if the characteristic times are similar. This resonance leads to an increase in membrane fluctuations, and to a decrease of the adhesiveness of the membranes.

This resonance effect may also be used to control cell adhesion on biomimetic surfaces. In recent years, synthetic molecules have been developed that can be switched, using light, between different conformations. The switching times of such molecules depend on the light intensity. Anchored at a substrate, the molecules can be used to switch the adhesive substrate properties and, thus, to manipulate and study cell adhesion.