Nano-particles carried by multiple dynein motors self-regulate their number of actively participating motors.

Abstract

The application of nanotechnology in medicine is expected to spread rapidly. Many substances are now being researched for drug delivery and, more especially, cancer therapy and dealing with various viruses such as HIV, Herpes simplex virus, and adenoviruses. Since it is the center of gene maintenance and expression regulation, the cell nucleus is a valuable target for viruses of the type outlined above as well as drug delivery systems. The microtubule-associated motor protein dynein is primarily responsible for spontaneously occurring intracellular transport to the nucleus. In this case, we are inspired by viruses (for example, HIV) that recruit dyneins to actively move towards the nucleus. This type of transport is known as “active transport,” and it is distinguished by its directionality and persistence motion toward the nucleus, making it more effective... In this project we aim to mimic the highly efficient transportation properties of native cargoes by rationally designing universally decorated nano-particles (NPs) that could be used for drug delivery applications. We investigate the motion of artificial NPs which grafted with flexible polymers, each ending with a nuclear localization signal (NLS) peptide, thereby allowing recruitment of mammalian cytoplasmic dynein. This unique NP can self-regulate the number of participating dynein motor proteins to optimize their motility properties - engendering persistent motion towards the cell nucleus while being able to go around obstacles that are abundant in the cytoplasm or on the microtubules. Based on these benefits, the use of active transport rather than passive transport has a promising future for therapeutic reasons, both in terms of treatment efficiency and reduced side effects, as the amounts of drug/DNA necessary for therapy are reduced.