Cells rely on molecular motors called dyneins to transport cargoes such as organelles and protein complexes along microtubules, the intracellular tracks that organize transport. In neurons, dynein-driven transport must function reliably over exceptionally long distances. Disruption of dynein activity is linked to severe neurological and developmental disorders.

Traditional structural models have suggested that dynein–dynactin transport complexes operate with a fixed composition, typically containing one or two dynein motors bound to a cargo adaptor. These models have largely been based on static structural snapshots and experiments performed in the absence of mechanical load.

In a study by researchers at Albert Einstein College of Medicine published online on February 16 in Nature Cell Biology, Arne Gennerich, Ph.D., Lu Rao, Ph.D., and colleagues show that dynein transport complexes are instead dynamic and respond to their mechanical load. Using single-molecule force measurements, fluorescence imaging, and structural analysis, the researchers demonstrate that mechanical tension can trigger the recruitment of an additional, third dynein motor into the dynein–dynactin complex. This load-induced assembly increases the force that the complex can generate, allowing it to adapt to rising mechanical demands.

This adaptive mechanism provides a new framework for understanding how intracellular transport remains robust, particularly in neurons, where transport failure has severe consequences. The findings also offer new insight into how disease-associated mutations may impair transport by disrupting force-dependent motor regulation.

Dr. Gennerich, the senior and corresponding author of the study, is professor of biochemistry at Einstein. Dr. Rao, a research assistant professor of biochemistry at Einstein, is first and co-corresponding author.