Compartmentalization of cellular processes into membrane-bound and membrane-less organelles is vital for cell function, enabling precise regulation of signaling, trafficking, and homeostasis. Recent discoveries have revealed the dynamic interplay between membrane-less organelles—known as biomolecular condensates—and membranes, highlighting their crucial role in coordinating cellular activities such as neurotransmitter release. We investigate the condensate-membrane interaction at the synapse using two condensate-forming proteins: synapsin-1, the most abundant soluble neuronal protein essential for clustering of synaptic vesicles, and PDZD8, an ER-resident protein critical for the formation of membrane contacts between ER and mitochondria. Our data indicate that lipid composition determines the level of interaction between both synapsin-1 and PDZD8 condensates with membranes. Moreover, we established 2D graphene sensors for characterizing electric properties of these condensates and discovered that condensates accumulate electric potential at their interfaces, suggesting the biomolecular condensates as the putative mesoscale capacitors. In fact, the acute disruption of cytosolic osmolarity led to the disruption of condensates morphology, indicating the dependance of condensates from local ion concentration. Nowhere is this dependance more relevant than in the context of neuronal synapses where activity-dependent depolarization leads to transient ion fluxes. Our cellular models and electrical sensors will help dissect how the changing environmental conditions impact the condensate-membrane signaling cascade.
Dragomir Milovanovic (Sun,) studied this question.