Figure 5

Schematic representation of the hypotheses proposed for the involvement of inflammasome components ASC, NLRP3 and AIM2 in macrophages responses to controlled nanotopography and chemistry.

We hypothesise that the increased levels of TNFα and IL-6 by ASC^−/− and NLRP3^−/− BMDM is due to membrane perturbations caused by the curvature of the nanoparticles, leading to Syk kinase activation as proposed by the membrane affinity triggered signalling model. This receptor-independent signalling may result in higher cytokine levels in the absence of inflammasome components capable of IL-1β secretion. In the case of AIM2^−/− BMDM, we hypothesise that cell perturbations on ‘rougher’ surfaces result in NLRP3 activation via mitochondrial dystunction and in addition to potentially higher levels of Akt in the absence of AIM2, these pathways enhance TLR signalling that control IL-1β release. The black text represents our hypotheses and the blue text represents the observations of this study.