Mathematical modeling of integrin dynamics in initial formation of focal adhesions

Abstract

Cellular motility is an important function in many cellular processes. Among the key players in cellular movement are transmembrane receptor proteins called integrins. Through the development of a mathematical model we investigate the dynamic relationship between integrins and other molecules known to contribute to initial cellular movement such as extracellular ligands and intracellular adhesion proteins called talin. Gillespie’s stochastic simulation algorithm was used for numerical analysis of the model. From our stochastic simulation, we found that most activity in our system happens within the first five seconds. Additionally we found that while ligand-integrin-talin complexes form fairly early in the simulation, they soon disassociate into ligand-integrin or integrin-talin complexes, suggesting that the former tertiary complex is less stable than the latter two complexes. We also discuss our theoretical analysis of the model and share results from our sensitivity analysis, using standardized regression coefficients as measures of output sensitivity to input parameters.