Molecular Force Imaging Reveals That Integrin-Dependent Mechanical Checkpoint Regulates Fc-Receptor-Mediated Phagocytosis in Macrophages

Macrophagesare a type of immune cell that helps eliminatepathogensand diseased cells. Recent research has shown that macrophages cansense mechanical cues from potential targets to perform effectivephagocytosis, but the mechanisms behind it remain unclear. In thisstudy, we used DNA-based tension probes to study the role of integrin-mediatedforces in Fc gamma R-mediated phagocytosis. The results showed thatwhen the phagocytic receptor Fc gamma R is activated, the force-bearingintegrins create a "mechanical barrier" that physicallyexcludes the phosphatase CD45 and facilitates phagocytosis. However,if the integrin-mediated forces are physically restricted at lowerlevels or if the macrophage is on a soft matrix, CD45 exclusion issignificantly reduced. Moreover, CD47-SIRP alpha "don'teat me" signaling can reduce CD45 segregation by inhibitingthe mechanical stability of the integrin barrier. These findings demonstratehow macrophages use molecular forces to identify physical propertiesand combine them with biochemical signals from phagocytic receptorsto guide phagocytosis.