Nonequilibrium biochemical structures in two space dimensions with local activation and regulation.

Abstract

Integrin receptor (IR) clustering is an example of pattern self-organization in biological systems. This paper describes a model for receptor activation whose content is guided by two major principles in cellular signal transduction: (i) Proteins cycle between different conformational states; (ii) the dynamics of their conformational dynamics is environment dependent. Based on a simple activation pathway where these two hypotheses are formulated in a self-consistent way, this paper focuses mainly on stochastic simulations valid in the limit of a small number of molecules. It is shown that coherent clustering can lead to digital signaling and receptor competition in biochemical systems where the model gives a recruitment mechanism for the reinforcement of the mechanical linkage with the extracellular matrix. Together with previous works, this paper provides a workable model for cell integrin adhesive structures when feedback mediated by membrane diffusing signals is dominant. Consequences are discussed in the framework of published data concerning the local production of a key phospholipid for cell signaling (PIP_{2}).