Many critical cell processes occur in the nucleus – the control center of the cell containing our DNA. However, in order for the nucleus to function correctly, movement of molecules such as proteins both in and out of the nucleus is necessary. The main gateway through which  molecules enter and leave the nucleus is the nuclear pore complex (NPC), a large protein structure on the outer shell of the nucleus that regulates the movement of molecules essential for cell function and gene regulation. 

How does the NPC control what goes in and what goes out? It has been previously believed that larger molecules are more challenging to translocate across the NPC. However, this turned out to only be half the story. In a recently published study in Nature Physics, researchers discovered that mechanical stability (i.e. how soft or stiff it is) of proteins significantly impacts their transportation across the NPC. Specifically, the authors show that proteins containing softer, more flexible regions translocate faster across the NPC as compared to stiffer proteins. Additionally, they show that the molecule size does not significantly impact the import rates of stiffer proteins, and that the mechanical stability of the molecule is the limiting factor for transport. To verify these observations, the researchers modified stiff proteins to have softer regions and showed this accelerated the translocation across the NPC, highlighting the sensitivity to protein mechanical properties.

This study enhances our  understanding of NPC transport by emphasizing the importance of the mechanical properties of translocating proteins and offering insights into the design of proteins with improved nuclear import rates. Understanding and manipulating this process can lead to significant advances in biotechnology and medicine, allowing us to provide improved drug delivery systems and targeted gene therapies to future patients.

This study was led by researchers at The Francis Crick Institute and King’s College London with corresponding author Sergi Garcia-Manyes.

Managing Correspondent: Gurminder K. Paink 

Press article: Research shows that ‘softer’ proteins can cross into the nucleus quicker (Phys.org)

Original Journal Article: Structural anisotropy results in mechano-directional transport of proteins across nuclear pores (Nature Physics)

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