Mechanical modulation of receptor-ligand interactions at cell-cell interfaces

Biophys J. 2012 Mar 21;102(6):1265-73. doi: 10.1016/j.bpj.2012.02.006. Epub 2012 Mar 20.


Cell surface receptors have been extensively studied because they initiate and regulate signal transduction cascades leading to a variety of functional cellular outcomes. An important class of immune receptors (e.g., T-cell antigen receptors) whose ligands are anchored to the surfaces of other cells remain poorly understood. The mechanism by which ligand binding initiates receptor phosphorylation, a process termed "receptor triggering", remains controversial. Recently, direct measurements of the (two-dimensional) receptor-ligand complex lifetimes at cell-cell interface were found to be smaller than (three-dimensional) lifetimes in solution but the underlying mechanism is unknown. At the cell-cell interface, the receptor-ligand complex spans a short intermembrane distance (15 nm) compared to long surface molecules (LSMs) whose ectodomains span >40 nm and these LSMs include phosphatases (e.g., CD45) that dephosphorylate the receptor. It has been proposed that size-based segregation of LSMs from a receptor-ligand complex is a mechanism of receptor triggering but it is unclear whether the mechanochemistry supports such small-scale segregation. Here we present a nanometer-scale mathematical model that couples membrane elasticity with the compressional stiffness and lateral mobility of LSMs. We find robust supradiffusive segregation of LSMs from a single receptor-ligand complex. The model predicts that LSM redistribution will result in a time-dependent tension on the complex leading to a decreased two-dimensional lifetime. Interestingly, the model predicts a nonlinear relationship between the three- and two-dimensional lifetimes, which can enhance the ability of receptors to discriminate between similar ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena / physiology
  • Cell Communication*
  • Ligands
  • Models, Biological
  • Protein Binding
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cell Surface / metabolism*
  • Time Factors


  • Ligands
  • Receptors, Antigen, T-Cell
  • Receptors, Cell Surface