Engineering physical microenvironments to study innate immune cell biophysics

Innate immunity forms the core of the human body's defense system against infection, injury, and foreign objects. It aims to maintain homeostasis by promoting inflammation and then initiating tissue repair, but it can also lead to disease when dysregulated. Although innate immune cells respond to their physical microenvironment and carry out intrinsically mechanical actions such as migration and phagocytosis, we still do not have a complete biophysical description of innate immunity. Here, we review how engineering tools can be used to study innate immune cell biophysics. We first provide an overview of innate immunity from a biophysical perspective, review the biophysical factors that affect the innate immune system, and then explore innate immune cell biophysics in the context of migration, phagocytosis, and phenotype polarization. Throughout the review, we highlight how physical microenvironments can be designed to probe the innate immune system, discuss how biophysical insight gained from these studies can be used to generate a more comprehensive description of innate immunity, and briefly comment on how this insight could be used to develop mechanical immune biomarkers and immunomodulatory therapies.