Neutrophils are the most abundant circulating white blood cell in the human body, and play a crucial role in the innate immune response to infection and inflammation. Sepsis is a systemic bacterial infection that results in a complex immune response. In this event, neutrophils are exposed to an excess of chemical stimuli that results in over activation. These over-activated neutrophils cause tissue damage, organ dysfunction, and death. In this project, I will study the change in cellular mechanisms between naïve and lipopolysaccharide (LPS)-activated neutrophils by quantifying the material displacement fields and surface tractions. This will provide information moving forward to understand the mechanical dysregulation that neutrophils undergo at a heightened activation state. This data will aid our understanding of neutrophil biochemical and mechanical sensing to recognize injury, and then migrate to the site of injury. In this study, I will identify the change in neutrophil motility and force generation before and after LPS activation. I use human fibronectin and human ICAM-1 coated on mechanically tunable polyacrylamide hydrogels (E=1.7 kPa and 8.7 kPa) to study naïve and LPS-activated neutrophils. By studying material displacement fields and surface tractions, the Franck Lab will better understand healthy and over-activated neutrophil motility and identify key phenotypic markers to detect and provide treatment in the event of sepsis. This will further help establish a baseline on the relationship between mechanics and cellular mechanisms, with a focus on neutrophil migration and adhesion.
Andrews, Christina,
"A Biophysical Analysis of Neutrophil Force Generation in a Biochemical Environment"
(2018).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.26300/131y-zg77
