@article{Individual:6510,
      recid = {6510},
      author = {Mulder, Elizabeth J},
      title = {Probing Individual and Collective Macrophage Responses  with Fluidic Force Microscopy},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2023-06},
      abstract = {Macrophages play a central role in the immune response by  monitoring for signs of infection and then initiating a  wider response. This immune response needs to be  proportionate to the threat; both over-responding and  under-responding are potentially dangerous to the body. The  number of macrophages that activate, the degree and  duration of their responses, and the types of signals they  generate may all impact the downstream immune response.  However, not all macrophages respond identically even to a  uniform stimulus, and macrophages residing in tissues  likely encounter localized and/or transient signals to  which individual cells may respond differently depending on  their context, history, cell state, etc. Within this  complex environment, how do macrophages calibrate their  individual and collective responses to correctly match  their response to the threat? Answering this question is  difficult with traditional experimental techniques that  either treat an entire culture or isolate cells from their  environment. Fluidic Force Microscopy (FluidFM) combines  the precision control of Atomic Force Microscopy (AFM) with  a pneumatic system capable of delivering picoliter volumes  of liquid through a hollow AFM probe. FluidFM stimulation  targets cells on their length-scale, allows simultaneous  live cell monitoring, preserves environmental context, and  gives the user precise control over the location,  concentration, and duration of stimulation. Using the  FluidFM, I determined the minimum conditions in  concentration and time for activation of single macrophages  via TLR stimulation, compared single, small group, and  whole culture stimulation, and found a dependence on  culture density in modulating the group response. I built a  model to determine the stimulus gradients produced by  FluidFM dispensing and how it related to the spatial limits  of the macrophage group response. Lastly, I developed a  method to investigate whole pathogen-macrophage  interactions with the FluidFM, in order to determine the  physical parameters that are necessary to generate an  immune response. This research advances our knowledge of  how macrophages, singly and collectively, modulate their  responses to signs of infection and environmental factors.  These regulation strategies by early-responding cells are  one piece of how the whole immune system regulates itself  for safe and effective function. Note: supplementary data  and code files from this research can be found online at:  DOI 10.17632/mfyddz6n8k.1},
      url = {http://knowledge.uchicago.edu/record/6510},
      doi = {https://doi.org/10.6082/uchicago.6510},
}