Modeling cellular adhesion

Cellular adhesion strength, described by the fraction of cells that detach from a surface for a range of applied shear stresses, is predictive of cancer cell migration in 2D and 3D environments and the overall metastatic potential of these cells. Simply stated, cell adhesion strength depends on the balance between cell-surface bond formation and breakage rates. This has been previously modeled as such using the concentration of adhesion proteins such as integrins, the cell-surface interaction area, and a shear force dependent bond breakage rate between the surface ligands and adhesion proteins. However, we have shown that changes in intracellular myosin motor activity, actin stress fibers and force responsive focal adhesion complex proteins can also influence cell adhesion strength and alter cell migration behavior. Using a computational model, we explore how various intracellular factors beyond the concentration of adhesion proteins, govern cell adhesion strengths as measured by shear flow analysis. Overall, our model focuses on 5 key cytoskeletal aspects and their impact on cellular adhesion because of their apparent relevance from previous studies. These include: average number of stress fibers per cell (dictated by f-actin and myosin concentrations), available integrins per stress fiber (dictated by integrin concentration and actin branching), likelihood of bound paxillin, active myosin motors (dictated by myosin light chain phosphorylation), and finally actin polymerization and depolymerization dynamics (governed by time between depolymerization and repolymerization events). The model is further used as a predictive tool in order to determine the particular intracellular factors differentiating cancer strains. The goal of this research is to unravel biomechanical and consequently biochemical differences between cytoskeletal elements of highly metastatic and non-metastatic cancer cells.