Engineering physical microenvironments to study innate immune cell biophysics

Abstract

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.

Substrate viscoelasticity affects human macrophage morphology and phagocytosis

“…12 However, the effects of viscoelasticity on macrophages are currently unknown despite them being equally responsive to their physical microenvironment. [13][14][15] In fact, mouse bone marrow-derived macrophages cultured in confinement on fibronectin adhesive spots adopt an anti-inflammatory phenotype 16,17 and human THP-1 model macrophages grown on stiff collagencoated PAA substrates become less phagocytic. 18 Given their central role in orchestrating tissue-wide responses 19,20 such as inflammation and fibrosis, these observations further suggest that homeostasis or disease progression may be controlled by biophysical macrophage-matrix interactions.…”