The main objective of this proposal is to apply emerging technologies in developing multi-scale computational approaches for studying heterotypic cell-cell collision and adhesion to a substrate under dynamic shear forces. In particular, the focus is on leukocyte (PMN)-melanoma cell emboli formation in a non-linear shear flow and subsequent tethering to the vascular endothelium (EC) as a result of cell-cell aggregation. The extent of tumor cell adhesion to a vessel wall is governed by the kinetic formation/disruption of receptor ligand bonds, the hydrodynamic shear and the heterotypic cell populations within the circulation. The project will provide understanding for the complex role of micro-hemodynamics, heterotypic cell populations, secreted chemokines, and PMN-melanoma adhesion in the recruitment of metastatic cancer cells to the EC in the microcirculation. A multi-scale computational fluid dynamics (CFD) code will be applied to perform direct numerical simulation, where each cell in the system is explicitly resolved.
This research will promote new crossdisciplinary approaches in research and education, integrating biomedical engineering, physical sciences and life sciences. The research results will be actively disseminated, using timely publications in the research literature as well as through the investigator's web sites and seminar lectures. The investigators will foster education through the application of engineering principles to cell biology, integrated with applied mathematics, mechanics, computational science, bioengineering and medical sciences.
Computational tools have become increasingly important in enabling progress in biomedical research. The objective of this proposal has applied emerging technologies in developing multi-scale computational approaches for studying heterotypic cell-cell collision and adhesion to a substrate under dynamic shear forces. In particular, we have focused on leukocyte (PMN)-melanoma cell emboli formation in a non-linear shear flow and subsequent tethering to the vascular endothelium (EC) as a result of cell-cell aggregation. The kinetic formation/disruption of receptor ligand bonds, the hydrodynamic shear and the heterotypic cell populations within the circulation govern the extent of tumor cell adhesion to a vessel wall. Intellectual merits have revolved understanding the complex role of micro-hemodynamics, heterotypic cell populations, secreted chemokines, and PMN-melanoma adhesion in the recruitment of metastatic cancer cells to the EC in the microcirculation; while broad impacts are significant by our accomplishment in fostering new cross-disciplinary approaches in research and education, integrating biomedical engineering, physical sciences and life sciences. We will expect our results be the ultimate end users of the projects of this multi-scale computational and experimental research. Research results have been actively disseminated, using timely publications in the research literature as well as through our web sites, seminar lectures. We have successfully fostered education through the application of engineering principles to cell biology, integrated with applied mathematics, mechanics, computational science, bioengineering and medical sciences.
