(521g) Invited: When Cells Meet: Rules of (cell) Engagement in Cancer Progression and Tissue Engineering

Authors: 
Asthagiri, A. - Presenter, Northeastern University
There is a flurry of cellular activity and movement in microenvironments, such as a tumor or an implanted bioengineered scaffold. Many cells and cell types migrate and invade through these environments, with various agendas, some malignant. In crowded environments, it is commonplace for migrating cells to encounter other cells along their path. How cells respond to cell-cell “collisions” is a fundamental question, with important implications for cancer progression or biomaterial colonization. In breast cancer, cancer cells migrate along collagen fibrils. Whether colliding cancer cells stop migrating and reverse direction, or circumnavigate and slide past each other, will affect the efficiency of invasion. If collisions occur on average more often than the persistence time of random walks, the mean free path of random walk is affected by the response to collisions. Similarly, as cells infiltrate a biomaterial, how frequently a cell turns around every time it encounters another cell will affect kinetics of material colonization. I will describe our lab's progress in investigating how migrating cells respond to cell-cell encounters in confined microenvironments relevant to fibrillar biomaterials and tumor microenvironments. We find that the cell response is a quantitative balance between sliding versus retraction. Genetic regulators relevant to cancer progression (ErbB2, E-cadherin, PARD3, TGFβ) and physical factors (degree of spatial confinement, cell size, fiber width) influence the response. We have devised and demonstrated a framework to measure the combined effect of genetic and physical factors along a common quantitative “ruler”. Our findings provide an understanding of how genetic and physical microenvironmental factors conspire to promote cancer progression and how biomaterials may be designed to facilitate colonization by exploiting the rules of cell engagement.