A Computational Study of the Dynamics of Cadherin-Catenin Complex Regulated by Actin Cytoskeleton

Abstract

Cadherin ligations activate many intracellular signaling cascades that govern cell and tissue behaviors. For example, cadherin homophilic interactions lead to structural reorganization of actin networks in a Rho-dependent manner. Interestingly, actin filaments can also affect cadherin dynamics by anchoring the cadherin-catenin complex (CCC) and limiting the diffusion of CCC. Despite experimental efforts, a mechanistic analysis of interactions between CCC and actin structures does not exist because both systems are highly dynamic and complex. In this study, we probed how cadherin dynamics is regulated by actin filaments using a coarse-grained computational model. We found that CCC movement is inhibited to an extent depending on actin concentration and average filament length, resulting in different cluster size and lifetime. We also showed that the number of actin available for CCC binding outcompetes the binding affinity between CCC and actin filaments. This implies the importance of vinculin which can link CCC to a deeper and larger actin pool beneath the cell membrane. We further tested the hypothesis that actin turnover accelerates cadherin cluster disassembly by competing with cis interactions. Our model sheds light on the interactions between the actin cytoskeleton and cell adhesion molecules and also pave the way for future studies with detailed and additional cellular circumstances taken into consideration.