Parallel lipoplex folding pathways revealed using magnetic tweezers.

摘要: Lipid-coated DNA nanoparticles (lipoplexes) are a powerful gene delivery tool with promising therapeutic applications. The mechanism of lipoplex assembly remains poorly understood. We explored packing by cationic lipid DSTAP (distearoyl trimethylammonium-propane) using magnetic tweezers. DSTAP-induced condensation occurred as series bursts the mean step size 60 nm to 80 nm. pause time preceding steps could be approximated bimodal distribution, which reveals at least two distinct pathways. rapidly condensed was more resilient force-induced decondensation. proportion stable, fast-formed complexes decreased high salt concentrations. A similar trend observed in bulk experiments. Lipoplexes assembled low concentration efficiently shielded from fluorescent dyes and DNase even after transfer conditions. These data reveal that folding occurs via parallel pathways single molecule level. progress through can monitored real manipulations. relative efficiency varied external