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Self-assembled materials capable of modulating their assembly properties in response to specific enzymes play a pivotal role in advancing ‘intelligent’ encapsulation platforms for biotechnological applications. Here, we introduce a previously unreported class of synthetic nanomaterials that programmatically interact with histone deacetylase (HDAC) as the triggering stimulus for disassembly. These nanomaterials consist of co-polypeptides comprising poly (acetyl L-lysine) and poly(ethylene glycol) blocks. Under neutral pH conditions, they self-assemble into particles. However, their stability is compromised upon exposure to HDACs, depending on enzyme concentration and exposure time. Our investigation, utilizing HDAC8 as the model enzyme, revealed that the primary mechanism behind disassembly involves a decrease in amphiphilicity within the block copolymer due to the deacetylation of lysine residues within the particles’ hydrophobic domains. To elucidate the response mechanism, we encapsulated a fluorescent dye within these nanoparticles. Upon incubation with HDAC, the nanoparticle structure collapsed, leading to controlled release of the dye over time. Notably, this release was not triggered by denatured HDAC8, other proteolytic enzymes like trypsin, or the co-presence of HDAC8 and its inhibitor. We further demonstrated the biocompatibility and cellular effects of these materials and conducted a comprehensive computational study to unveil the possible interaction mechanism between enzymes and particles. By drawing parallels to the mechanism of naturally occurring histone proteins, this research represents a pioneering step toward developing functional materials capable of harnessing the activity of epigenetic enzymes such as HDACs. 

Abstract To evaluate the mechanisms driving nanoscale trace element mobility in radiation-damaged zircon, we analyzed two well-characterized Archean zircons from the Kaapvaal Craton (southern Africa): one zircon remained untreated and the other was experimentally heated in the laboratory at 1450 °C for 24 h. Atom probe tomography (APT) of the untreated zircon reveals homogeneously distributed trace elements. In contrast, APT of the experimentally heated zircon shows that Y, Mg, Al, and Pb+Yb segregate to a set of two morphologically and crystallographically distinct cluster populations that range from 5 nm tori to 25 nm toroidal polyhedra, which are confirmed to be dislocation loops by transmission electron microscopy (TEM). The dislocation loops lie in {100} and {001} planes; the edges are aligned with <100>, <101>, and <001>. The largest loops (up to 25 nm diameter) are located in {100} and characterized by high concentrations of Mg and Al, which are aligned with <001>. The 207Pb/206Pb measured from Pb atoms located within all of the loops (0.264 ± 0.025; 1σ) is consistent with present-day segregation and confirms that the dislocation loops formed during our experimental treatment. These experimentally induced loops are similar to clusters observed in zircon affected by natural geologic processes. We interpret that differences in cluster distribution, density, and composition between experimentally heated and geologically affected zircon are a function of the radiation dose, the pressure-temperature-time history, and the original composition of the zircon. These findings provide a framework for interpreting the significance of clustered trace elements and their isotopic characteristics in zircon. Our findings also suggest that the processes driving cluster formation in zircon can be replicated under laboratory conditions over human timescales, which may have practical implications for the mineralogical entrapment of significant nuclear elements.