Investigating DC migration with large, ingested cargos through confining environments

forthcoming

As immune sentinels, dendritic cells (DCs) must be able to ingest material and migrate to lymph nodes to present the processed antigen to T cells, and initiate the adaptive immune response, essential against pathogens or cancer. This means that DCs must be able to navigate through complex environments with this ingested material of varying physical characteristics. Preliminary data revealed that DCs deform and/or rotate large, ingested material to overcome occlusion from entering constriction points (transmigration). Additionally, there are instances of nuclear deformation and even migratory frustration, which reflect reported phenomena of DCs in vivo in mice. I propose to use a suite of fabricated particles and in vitro complex environments to test the ability of mouse bone marrow-derived dendritic cells to overcome physical obstacles with large cargos. The fabricated particles will include oil droplets with tunable deformability, paramagnetic particles, and 3D printed microplastics. The in vitro complex environments are collagen gels and PDMS microchannels where I can observe DCs with ingest particles attempting to through points of constriction. With this experimental set-up, I can measure the efficiency of transmigration, deformation or rotation of particles, as well as the force exerted on particles as a function of particle properties. Furthermore, I can observe the effect of particle manipulation on DC behavior and function, even if they never successfully transmigrate. This work will aim to answer how dendritic cells can migrate successfully with a wide range of materials, but also provide insight into the role of frustrated or trapped DCs that are observed in tissues, and particularly near tumors.