The nucleus is extensively studied for its role in gene expression. However, growing evidences indicate that the biophysical properties of this organelle participate in cellular functions such as cell migration and pathogen killing; two processes critical for immune response. In this talk, I will describe our discovery of how immune cells undergoing confined migration squeeze their nuclei through narrow pores by forming a dense perinuclear actin network. I will also describe how we uncovered the temporally conserved sequence of cellular events allowing neutrophils to burst their nuclei and release their DNA to the extracellular environment to kill pathogens during NETosis. My work, by revealing the cellular events driving NETosis, opens new and exiting avenues for understanding the cellular biophysics of this intriguing immune response.