Mechanical actuators in microglia dynamics and function

Microglia are the most prominent immune resident cell population in the central nervous system (CNS). In the healthy CNS, microglia survey their surrounding microenvironment, through recurrent extension and retraction of filopodia-like membrane protrusions, without evident cell body displacement. Microglia undergo dramatic transcriptomic and shape changes upon brain insults or neurodegenerative disease states and adopt a classical immune effector function (producing an extensive array of inflammatory mediators such as cytokines, chemokines, and reactive oxygen species) to re-establish tissue homeostasis. While the biophysical principles underlying microglia morphological changes remain elusive, several recent studies have highlighted the pivotal role of the actin and non-muscle myosin II filamentous cytoskeleton in this process. In this work, we discuss how subcellular topological patterning of the actin and myosin cytoskeleton can control microglial cell shape dynamics and how it can potentially feedback on their functional specialization, which is of great importance to understanding the mechanisms of microglial action in homeostatic conditions and CNS disease states.