Integrin clustering in two and three dimensions.
Integrins are transmembrane proteins that allow cells to bind to their external environment. They are the primary regulators of cell-matrix interactions, with direct roles in cell motility and signaling, which in turn regulate numerous physiological processes. Under common experimental conditions, integrins tend to cluster for sturdy and effective binding to extracellular matrix molecules. These clusters often evolve into focal adhesions, which regulate downstream signaling. However, integrin clusters are more pronounced and have longer lifetimes in two-dimensional assays than in more realistic three-dimensional environments. While a number of models and theoretical approaches have focused on integrin binding and diffusion, the reasons for the differences between two- and three-dimensional clustering have remained elusive. In this study, we model an individual cluster attached to a two-dimensional collagen film and attached to collagen fibers of various sizes in three-dimensional matrices. We then discuss how our results explain differences in size and lifetime, and how they hint at reasons for other differences between the two environments. Further, we make predictions regarding the stability of clusters based on different overall intracellular conditions. Our results show good agreement with experiments and provide a quantitative basis for understanding how matrix dimensionality and structure regulate integrin behavior in environments that mimic in vivo conditions.
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA. lep@bu.edu
David
D
Lepzelter
Oliver
O
Bates
Muhammad
M
Zaman
D000818:Animals; D055592:Biophysical Phenomena; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology; D003094:Collagen / Q000737:chemistry / Q000502:physiology; D003198:Computer Simulation; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000502:physiology; D016023:Integrins / Q000737:chemistry* / Q000502:physiology; D008958:Models, Molecular; D009010:Monte Carlo Method; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization
D016326:Extracellular Matrix Proteins; D016023:Integrins; D003094:Collagen