Physical principles underlying cadherin‐mediated cell‐cell recognition

Abstract

A variety of cell‐cell adhesion processes are mediated by the (trans) dimerization of cadherin proteins presented from apposing cell surfaces. A multiscale combined experimental/theoretical approach to this general problem will be described with particular focus on the development of a correlation between measured binding affinities at the molecular level and cell‐cell adhesive specificity. Following cell‐cell contact, cadherin dimers cluster together to form cell‐cell junctions. Since such clustering does not occur in the absence of cell‐cell contact, there is a necessary coupling between trans and lateral (cis) interactions. The molecular mechanism that underlies this coupling will be discussed and is characterized in detail through combination of x‐ray crystallography and coarse grained simulations. In addition to the insights that will be discussed in the context of cadherin function, general principles that may underlie the molecular basis of many cell‐cell adhesion processes will be proposed. This work was supported by NSF, MCB‐0918535