Impact of receptor-ligand distance on adhesion cluster stability.
Cells in multicellular organisms adhere to the extracellular matrix through two-dimensional clusters spanning a size range from very few to thousands of adhesion bonds. For many common receptor-ligand systems, the ligands are tethered to a surface via polymeric spacers with finite binding range, thus adhesion cluster stability crucially depends on receptor-ligand distance. We introduce a one-step master equation which incorporates the effect of cooperative binding through a finite number of polymeric ligand tethers. We also derive Fokker-Planck and mean field equations as continuum limits of the master equation. Polymers are modeled either as harmonic springs or as worm-like chains. In both cases, we find bistability between bound and unbound states for intermediate values of receptor-ligand distance and calculate the corresponding switching times. For small cluster sizes, stochastic effects destabilize the clusters at large separation, as shown by a detailed analysis of the stochastic potential resulting from the Fokker-Planck equation.
Erdmann
T
T
University of Heidelberg, Im Neuenheimer Feld 293, 69120, Heidelberg, Germany.
Schwarz
U S
US
D001665:Binding Sites; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D021982:Cell-Matrix Junctions; D016000:Cluster Analysis; D005109:Extracellular Matrix / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D013269:Stochastic Processes
D015815:Cell Adhesion Molecules; D008024:Ligands