Journal
JOURNAL OF COMPUTATIONAL PHYSICS
Volume 244, Issue -, Pages 264-278Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcp.2012.09.010
Keywords
Integrin; Integrin clustering; Focal adhesions; Cellular mechanotransduction; Computational physics; Multiscale; Agent-based modeling
Funding
- National Science Foundation [CBET-0955291]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0955291] Funding Source: National Science Foundation
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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.
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