Search for: All records

Alpha-synuclein is a presynaptic protein linked to Parkinson’s disease with a poorly characterized physiological role in regulating the synaptic vesicle cycle. Using RBL-2H3 cells as a model system, we earlier reported that wild-type alpha-synuclein can act as both an inhibitor and a potentiator of stimulated exocytosis in a concentration-dependent manner. The inhibitory function is constitutive and depends on membrane binding by the helix-2 region of the lipid-binding domain, while potentiation becomes apparent only at high concentrations. Using structural and functional characterization of conformationally selective mutants via a combination of spectroscopic and cellular assays, we show here that binding affinity for isolated vesicles similar in size to synaptic vesicles is a primary determinant of alpha-synuclein-mediated potentiation of vesicle release. Inhibition of release is sensitive to changes in the region linking the helix-1 and helix-2 regions of the N-terminal lipid-binding domain and may require some degree of coupling between these regions. Potentiation of release likely occurs as a result of alpha-synuclein interactions with undocked vesicles isolated away from the active zone in internal pools. Consistent with this, we observe that alpha-synuclein can disperse vesicles from in vitro clusters organized by condensates of the presynaptic protein synapsin-1. 

Abstract Chemical energy ferroelectrics are generally solid macromolecules showing spontaneous polarization and chemical bonding energy. These materials still suffer drawbacks, including the limited control of energy release rate, and thermal decomposition energy well below total chemical energy. To overcome these drawbacks, we report the integrated molecular ferroelectric and energetic material from machine learning-directed additive manufacturing coupled with the ice-templating assembly. The resultant aligned porous architecture shows a low density of 0.35 g cm⁻³, polarization-controlled energy release, and an anisotropic thermal conductivity ratio of 15. Thermal analysis suggests that the chlorine radicals react with macromolecules enabling a large exothermic enthalpy of reaction (6180 kJ kg⁻¹). In addition, the estimated detonation velocity of molecular ferroelectrics can be tuned from 6.69 ± 0.21 to 7.79 ± 0.25 km s⁻¹by switching the polarization state. These results provide a pathway toward spatially programmed energetic ferroelectrics for controlled energy release rates.