Surface fluidity of membrane-bound cargoes enhance their ability to navigate roadblocks

Neurodegenerative diseases like the Alzheimer’s and Parkinson's disease involve disruption of intracellular transport due to the precence of different kinds of roadblocks on microtubule lattice, which include Microtubule Associated Proteins (MAPs) such as the tau protein. More generally, a variety of decorating proteins, stalled motors or cargo or other structures in the crowded cytoplasm can act as roadblocks. To explore the mechanisms available for cargoes to get past such roadblocks, we developed a Brownian dynamics simulation of membrane-bound cargo transport by teams of kinesin motors along microtubules that are populated with different kinds of roadblocks. Our previous work has shown that motor diffusivity on the membrane-bound cargo surface reduces the inter-motor interference and enhances run length in a co-operative and ATP dependent manner. Here we show that membrane-bound cargoes also have a higher probability of crossing roadblocks than membrane-free cargoes under specific conditions. Our results could have implications for the development of efficient treatments for neurodegenerative diseases.