Membrane Topography-Driven Movement of Biomolecular Condensates

Biomolecular condensates are assemblies of proteins or nucleic acids that exhibit liquid-like properties and organize intracellular biochemical reactions within many cells. Some condensates require membrane association, and we previously developed an assay to reconstitute biomolecular condensates in the presence of different membrane topographies. However, the effect of membrane topography on the displacement of biomolecular condensates remains incompletely understood. Here, we studied the movement of biomolecular condensates on lipid membrane-clad microstructures in a cell-free assay. We observed upward movements within microgrooves for untethered condensates. Increased membrane attachment reduced the number of upward movements. Further increasing the membrane attachment led to the formation of elongated condensates. We demonstrated a coordinated sideward movement of these elongated condensates. Finally, we found that molecular crowding with Ficoll70 decreased the frequency of upward movements by slowing condensate growth. Our results indicate that membrane topographies, in combination with membrane attachment patterns, regulate passive biomolecular condensate movement.