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Membrane fluctuations and acidosis regulate cooperative binding of “marker of self” CD47 with macrophage checkpoint receptor SIRPα | Journal of Cell Science
Membrane fluctuations and acidosis regulate cooperative binding of “marker of self” CD47 with macrophage checkpoint receptor SIRPα
Cell-cell interactions that result from membrane proteins binding weakly in trans can cause accumulations in cis that suggest cooperativity and thereby an acute sensitivity to environmental factors. The ubiquitous “marker of self” protein CD47 binds weakly to SIRPα on a macrophage, which leads to accumulation of SIRPα at a phagocytic synapse and ultimately to inhibition of engulfment of ‘self’ cells - including cancer cells. We reconstituted this macrophage checkpoint with CD47-GFP displayed on giant vesicles generated from plasma membranes and then imaged vesicles adhering to SIRPα immobilized on a surface. CD47 diffusion is impeded near the surface, and the binding-unbinding events reveal cooperative interactions as a concentration-dependent, two-dimensional affinity. Membrane fluctuations link cooperativity to membrane flexibility with suppressed fluctuations in the vicinity of bound complexes. Slight acidity (pH=6) stiffens membranes, diminishes cooperative interactions, and also reduces ‘self’ signaling of cancer cells in phagocytosis. Sensitivity of cell-cell interactions to microenvironmental factors - such as the acidity of tumors and other diseased or inflamed sites - can thus arise from collective, cooperative properties of membranes.
You are going to email the following Membrane fluctuations and acidosis regulate cooperative binding of “marker of self” CD47 with macrophage checkpoint receptor SIRPα