An agent based model of integrin clustering: Exploring the role of ligand clustering, integrin homo-oligomerization, integrin-ligand affinity, membrane crowdedness and ligand mobility

Authored by Yousef Jamali, Mohammad R. K. Mofrad, Tahereh Jamali

Date Published: 2013-07-01

DOI: 10.1016/j.jcp.2012.09.010

Sponsors: United States National Science Foundation (NSF)

Platforms: No platforms listed

Model Documentation: Other Narrative Mathematical description

Model Code URLs: Model code not found

Abstract

Integrins are cell-surface protein heterodimers that coordinate cellular responses to mechanochemical cues from the extracellular matrix (ECM) and stimulate the assembly of small adhesion complexes, which are the initial sites of cell-ECM adhesion. Clustering of integrins is known to mediate signaling through a variety of signal transduction pathways. Yet, the molecular mechanisms of integrin clustering are poorly understood. In this paper, we develop computational models, using agent based modeling (ABM) techniques, to explore two key underlying mechanisms of integrin clustering, namely ligand organization and integrin homo-oligomerization. Our models help to shed light on the potential roles ligand clustering and integrin homo-oligomerization may play in controlling integrin clustering. A potential mechanism for the clustering of integrin is discussed and the effects of other parameters such as integrin-ligand affinity, membrane crowdedness and ligand mobility on integrin clustering are examined. (C) 2012 Elsevier Inc. All rights reserved.

Tags

Agent-based modeling Multiscale Cellular mechanotransduction Computational physics Focal adhesions Integrin Integrin clustering