We are currently attempting to understand how the basic processes of contractility, protrusion and adhesion are integrated to produce cell migration. This is an intellectually challenging problem that requires new approaches. The overall plan is to test an in silico model developed by A. Mogilner and colleagues for migration and check this model by perturbing these basic processes locally using photomanipulative techniques to see if the experimentally determined changes in migration can be accounted for by the model. The feasibility of two types of perturbations has now been demonstrated. Caged actin binding proteins and peptides derived from Focal Adhesion Kinase (FAK) can be uncaged and produce dramatic phenotypes. A complementary loss of function technique, EGFP-chromophore-assisted laser inactivation (EGFP-CALI), has been applied locally to several actin binding proteins including EGFP-a-actinin, EGFP-Mena and EGFP-capping protein, again with strong phenotypes. Photochemical mechanisms mediating CALI will be discussed. I will also describe a graph theoretic approach to modeling motile phenomena that has been developed in collaboration with Gabriel Weinreb, Maryna Kapustina and Tim Elston. The causal map (CMAP) is a course-grained biological network tool that permits description of causal interactions between the elements of the network which leads to overall system dynamics. On one hand, the CM CMAP is an intermediate between experiments and physical modeling, describing major requisite elements, their interactions and paths of causality propagation. On the other hand, the CMAP is an in independent tool to explore the hierarchical organization of cell and the role of uncertainties in the system. It appears to be a promising easy-to-use technique for cell biologists to systematically probe v verbally formulated, qualitative hypotheses. We apply the CMAP to study the phenomenon of contractility oscillations in spreading cells in which microtubules have been depolymerized. Supported by the NIH Cell Migration Consortium, IK54GM64346.