Open your (nano)pores

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Open your (nano)pores

Nanoscale channels spanning biological membranes, transmembrane nanopores are everywhere. From the nucleus of a cell to your trusty Nanopore sequencer, protein pores are vital in biology and are becoming big players in biotech. Think DNA sequencing, peptide analysis, or even water filtration.

The catch? These pores are usually small, and they don’t allow the passage of bigger molecules (read: therapeutics). And if we have made some huge leaps in de novo protein design (did someone say AI?), engineering large protein nanopores remains tough.

You know what’s not hard to engineer? DNA origami. Okay, it is hard, but it’s a whole lot easier. Today’s paper introduces the MechanoPore. DNA nanopores have been around, but they were mainly static: you would decide the diameter at the design stage, and that was it. The MechanoPore, on the other hand, can switch back and forth between 3 configurations:

• Closed, with a diameter of only 10 nm

• Intermediate, with a diameter of 20 nm

• Open, with a hole sized at around 30 nm

The opening and closing of this rhombic pore is controlled by simple strand-displacement. Using DNA-PAINT, the team checked the switching, confirming that the structure held up after six rounds of changes. Next, they incorporated them into lipid membranes, and tested how well they could sort molecules by size. The different configurations of the pores allowed to selectively and reversibly what could enter the lipid vesicle: only small molecules when closed, and larger ones when open.

I find this work very cool. Custom nanopores like the MechanoPore could have huge implications across multiple fields:

• Drug delivery: Controllable nanopores could allow precise control over drugs entering a cell, a major challenge for larger or non-polar molecules.

• Synthetic biology: Nanopores are fundamentally for cellular life, so having reliable channels for macromolecule transport is a key step in building synthetic cells.

• Sensing and sorting: The MechanoPore could be a powerful tool for biosensing and molecular sorting, easily distinguishing between different biomolecules with one versatile structure.

So, go read the complete article here!

In other news:

• Switching back DNA? New forms of DNA are interesting, but their characteristics are not easy to determine. This study focuses on switchback DNA, a globally left-handed structure made of two parallel strands. Interestingly, switchback DNA has slower thermodynamic stability and needs higher magnesium levels for assembly but offers better biostability against some nucleases

• CRISPR for high schoolers: CRISPR has revolutionized research, but hands-on learning is not cheap, and often out of reach in educational settings. Here, the team developed CRISPRkit as an affordable, biosafe, and user-friendly kit for high school education, requiring no specialized equipment and costing around $2 per experiment. Hopefully coming soon to a classroom near you.

• Predicting EtBr effects: Modeling the effect of DNA-binding molecules is tough, but it holds potential for biological and therapeutic uses. In this work, the authors presents a method to simulate these changes, so you can predict how much worse your structure will look after gel extraction.

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