Nanoscale co-condensation and stretch resistance of FUS and DNA

Protein-DNA co-condensates where protein and DNA condensates colocalize, formed through liquid-liquid phase separation, play critical roles in gene expression, cancer, and developmental defects. Recent experimental studies have revealed the impact of mechanical stress on these co-condensates, but their dynamic processes and microscopic structures remain poorly characterized. Using coarse-grained molecular dynamics simulations, we investigated the nanoscale natures of FUS and DNA co-condensation under DNA stretching. We show that FUS and DNA contribute differently to co-condensation. Phase separation and superhelical structures lead to lag during the stretching-induced disruption of co-condensates, where lag refers to a delayed structural response that persists for a period before transition. The influence of pulling force on co-condensation displays a step-like pattern, and increasing force can reduce superhelical levels. These findings elucidate the mechanisms underlying the response of FUS-DNA co-condensation to mechanical stress and provide new insights into their regulatory roles in biological processes.