M.Sc Thesis

M.Sc StudentWiener Guy
SubjectCellular Mechanics in the Initial Stages of 3D Cancer
Cell Invasion
DepartmentDepartment of Biomedical Engineering
Supervisor ASSOCIATE PROF. Daphne Weihs
Full Thesis textFull thesis text - English Version


Metastatic cells adhere, invade and move through tissue and matrix by utilizing distinct internal and external mechanics. Dynamical mechanics of the cytoskeleton, morphological changes and biochemical remodeling of the extracellular matrix (ECM) facilitate cell migration and invasion in 3-dimentions (3D). We have recently observed that the leading edge of a metastatic cell indents a 3D non-degradable, impenetrable, non-physiological polyacrylamide gel. The degree of penetration was found to be correlated with the metastatic potential of the cells.  We suggest that the same phenomenon exists in physiological systems, at the initial stages of cell entrance into a 3D gel; as cells penetrate the surface of the gel. The focus of the following work was to create a robust experimental setup and analysis tool pack to test this hypothesis, and perform validation experiments. We have seeded high metastatic potential cells on physiologically-relevant collagen gel and recorded their time-dependent behaviors. The cells adhere within minutes to the gel, and over the course of several hours will deform and prepare to move into it. Throughout the course of this apparent invasion process, the cells are attached and applying a force which rises and falls with time. We use 3D image analysis to determine the force pattern applied by the cell relative to its morphology. An enhanced understanding of how and where forces are generated around the cell, and the effects that cytoskeleton-targeting drugs have on these forces, will revolutionize the concepts of metastatic invasion. Thus, new targets for diagnosis and treatment may be revealed. To achieve this, future directions are outlined based on the demonstrated feasibility of the setup and model that were developed herein.