A spatial model for integrin clustering as a result of feedback between integrin activation and integrin binding

Erik S. Welf, Ulhas P. Naik, Babatunde A. Ogunnaike

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Integrins are transmembrane adhesion receptors that bind extracellular matrix (ECM) proteins and signal bidirectionally to regulate cell adhesion and migration. In many cell types, integrins cluster at cell-ECM contacts to create the foundation for adhesion complexes that transfer force between the cell and the ECM. Even though the temporal and spatial regulation of these integrin clusters is essential for cell migration, how cells regulate their formation is currently unknown. It has been shown that integrin cluster formation is independent of actin stress fiber formation, but requires active (high-affinity) integrins, phosphoinositol-4,5-bisphosphate (PIP2), talin, and immobile ECM ligand. Based on these observations, we propose a minimal model for initial formation of integrin clusters, facilitated by localized activation and binding of integrins to ECM ligands as a result of biochemical feedback between integrin binding and integrin activation. By employing a diffusion-reaction framework for modeling these reactions, we show how spatial organization of bound integrins into clusters may be achieved by a local source of active integrins, namely protein complexes formed on the cytoplasmic tails of bound integrins. Further, we show how such a mechanism can turn small local increases in the concentration of active talin or active integrin into integrin clusters via positive feedback. Our results suggest that the formation of integrin clusters by the proposed mechanism depends on the relationships between production and diffusion of integrin-activating species, and that changes to the relative rates of these processes may affect the resulting properties of integrin clusters.

Original languageEnglish (US)
Pages (from-to)1379-1389
Number of pages11
JournalBiophysical Journal
Volume103
Issue number6
DOIs
StatePublished - Sep 19 2012

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Integrins
Cluster Analysis
Extracellular Matrix
Talin
Cell Movement
Physiological Feedback
Ligands
Stress Fibers
Extracellular Matrix Proteins
Cell Adhesion
Actins

ASJC Scopus subject areas

  • Biophysics

Cite this

A spatial model for integrin clustering as a result of feedback between integrin activation and integrin binding. / Welf, Erik S.; Naik, Ulhas P.; Ogunnaike, Babatunde A.

In: Biophysical Journal, Vol. 103, No. 6, 19.09.2012, p. 1379-1389.

Research output: Contribution to journalArticle

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