3D micro-environment regulates NF-κβ dependent adhesion to induce monocyte differentiation

Differentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-{kappa}{beta} activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signalling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. Our findings challenge the notion that adhesion is a result of monocyte differentiation. Rather its the adhesion which triggers the differentiation of monocytes. MAPK, and NF-{kappa}{beta} being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.\n\nSummary statementThis article brings out a new insight into the novel mechanisms of monocyte differentiation solely driven by physical micro-environment and adhesion.