SPIE/OSA Lecture: Jacob Notbohm
Abstract: Structural and mechanical properties of the extracellular microenvironment play a key role in development progression of disease. For example in breast cancer, aligned fibrous bands propagating outward from the boundary of a tumor are associated with a three-fold increase in the mortality rate. Such bands induce persistent directional migration of tumor cells and correlate with increased metastasis. The signal provided by those bands to induce migration is still unknown, but there have been proposed numerous mechanisms ranging from increased stiffness causing the cell to exert greater forces to the track-like path causing the cell to exert more directed forces. It remains difficult to separate these mechanisms from one another, because there is a lack of experimental technologies to study mechanical interactions between the cell and the microenvironment. We have developed new experimental tools to quantify and apply local displacements in a fibrous matrix. To measure cell-induced displacements, we embed cells into a matrix of fibrous collagen I and use confocal microscopy with quantitative image analysis. We find that cell-induced displacements propagate over a longer range than predicted by classical linear theories in mechanics. To apply local mechanical forces, we make particles of the active hydrogel poly(N-isopropylacrylamide), a material that undergoes a temperature-induced phase transition when heated above 32°C, causing a >50% decrease in volume. After embedding the particles in the collagen matrix and raising the temperature, the particles contract, closely mimicking the long-range displacement fields induced by contracting cells. With these experimental technologies, we are now testing cell response to mechanical forces and displacements in the microenvironment, for example by seeding both cells and contractile particles together and following the resulting cell response.