Author_Institution :
Med. Sch., Comput. Biol. Lab., Harvard Univ., Boston, MA, USA
Abstract :
Blood vessel growth is a fascinating and important example of an adaptive, morphologically plastic network formation process driven by complex interactions between individual cells in the vessel and between the cells and their dynamic extracellular environment. Under normal conditions this can generate a well-adapted hierarchical branching structure. However, in tumors, blood vessels become maladapted, leaky and bulbous, resulting in increased hypoxia and tumour cell metastasis. A method to switch tumor blood vessels back to a normal network could reduce metastasis and thus represents a significant goal in cancer therapy. However, studying human disease and the abnormalities that lead to pathological phenotypes is a monumentally difficult task. Probing the inner workings of in vivo systems present numerous technical challenges, though boundaries continue to be broken. Further, the normal fundamental mechanisms controlling development are of course not fully understood, let alone their perturbation by environmental changes in disease. Artificial Life (ALife) aims to instantiate and study biological principles of organisation in new media in order to exploit different methods to test the system uniquely available in that medium. Thus ALife can perfectly complement cutting edge in vivo research giving vital temporal, spatial and organisational understanding of the process, if we work together with biologists, to build data driven models, and test emergent properties. Using this integrated ALife/in vivo experimental approach, we have made advances in the understanding of blood vessel growth. The emergent properties of the embodied, agent-based model we developed, when put into a disease environment, have led to the discovery of a novel switch in cell communication which is changing the way we think about tumour malformations.
Keywords :
artificial life; blood vessels; cancer; medical diagnostic computing; tumours; agent-based model; artificial life; biological principle; blood vessel growth; cancer; cell communication; data driven model; disease environment; dynamic extracellular environment; hierarchical branching structure; human disease; hypoxia; morphologically plastic network formation process; pathological phenotypes; tumour cell metastasis; tumour malformation; Biological system modeling; Blood vessels; Cancer; Cells (biology); In vivo; Tumors; agent-based modelling; angiogenesis; artificial life; cancer; morphogenesis; simulation;