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-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signaling. 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. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.
statement: This article brings out a new insight into the novel mechanisms of monocyte differentiation solely driven by physical micro-environment and adhesion.2 Abstract: 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-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 microenvironment, 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 it's the adhesion which triggers the differentiation of monocytes. MAPK, and NF-being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like microenvironment would also influence other cellular functions. Introduction:Cellular functions are controlled by combinations of autonomous and non-autonomous factors. Non-autonomous factors elicit cellular responses via the cellular micro-environment.The chemical makeup of a cellular micro-environment imparts its response either via the receptor-ligand interaction at the plasma membrane or through the transport of soluble molecules into the cytoplasm. The physical makeup of the micro-environment also influences the functioning of the cells 1 2 3 4 . The functional heterogeneity in the macrophages associated with different tissues is speculated to arise from their heterogeneous micro-environments 5 6 .Inside an organism, cells encounter three distinct type of physical micro-environments i) 3D
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