Cell adhesion plays an indispensable role in coordinating physiological functions in multicellular organisms. During this process, specific types of cell adhesion molecules interact with each other from the opposite sides of neighboring cells. Following this trans-interaction, many cell adhesion molecules further aggregate into clusters through cis interactions. Beyond the molecule level, adhesion can be affected by multiple cellular factors due to the complexity of membrane microenvironments, including its interplay with cell signaling. However, despite tremendous advances in experimental developments, little is understood about the general principles of cell adhesion and its functional impacts. Here a mesoscopic simulation method is developed to tackle this problem. We illustrated that specific spatial patterns of membrane protein clustering are originated from different geometrical arrangements of their binding interfaces, while the size of clusters is closely regulated by molecular flexibility. Different scenarios of cooperation between trans and cis interactions of cell adhesion molecules were further tested. Additionally, impacts of membrane environments on cell adhesion were evaluated, such as the presence of a cytoskeletal meshwork, the membrane tension and the size effect of different membrane proteins on cell surfaces. Finally, by simultaneously simulating adhesion and oligomerization of signaling receptors, we found that the interplay between these two systems can be either positive or negative, closely depending on the spatial and temporal patterns of their molecular interactions. Therefore, our computational model pave the way for understanding the molecular mechanisms of cell adhesion and its biological functions in regulating cell signaling pathways.
ASJC Scopus subject areas
- Molecular Biology