Exploration of Durotaxis through Agent-Based Modeling
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Date
2015-05
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The Ohio State University
Abstract
Cell migration and remodeling of the extracellular matrix (ECM) play a critical role in many biological processes, including development, wound healing, fibrotic pathologies and tissue engineering. Although the importance of these processes has been recognized, a complete understanding of the mechanisms governing cell migration and remodeling of the ECM remain unclear. Specifically, the experimentally observed phenomenon in which cells migrate in the direction of increasing ECM stiffness, known as durotaxis, is not well understood. In order to gain an understanding of the mechanisms involved in durotaxis, an agent-based model (ABM) was developed in Netlogo. The resulting model provided two intuitive mechanisms for durotaxis. The first mechanism in which a cell retracts its pseudopods with a constant force was robust to different types of pseudopod extension and detachment from the ECM. The second mechanism in which a cell retracts its pseudopods with a spring force, was sensitive to the specific type of pseudopod extension and detachment from the ECM. It was also discovered that with a spring force, cells were not able to migrate once a maximum ECM stiffness threshold was reached. Results indicate that fine-tuning cellular and ECM parameters may allow for control of cell migration.
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Keywords
durotaxis, cell migration, agent-based modeling, cell mechanics, pseudopod, extracellular matrix