Researchers from the VIB-VUB Center for Structural Biology have pioneered a novel way to design custom transmembrane β-barrel nanopores, for greater control over the size and geometry of the pore in trying to enhance sensing and sequencing.

Partnering with the team with the University of Washington School of Medicine and others, the new method describes a Step Forward in Nanopore Design: For a long time now, nanopore technology has been promoted  as the much-awaited invention in the field of single-molecule DNA and RNA analysis. The small protein structures create pores in the lipid membranes, enabling big strides in portable sequencing equipment and diagnostics. 

Enter de novo protein design, this technique enables totally new transmembrane β-barrel pores can be designed by scientists with any desired property, including even size, geometry, and conductance levels. Using techniques such as nuclear magnetic resonance and crystallography, these pores have been proved to not only be stable but highly tunable by researchers. It possesses a diameter from 0.5 to 1.1 nanometers and conductance levels from 110 to 430 picosiemens. This technology could revolutionize sensing and sequencing in NGS and could be part of the next generation of Nanopore devices.

A New Benchmark

Probably the most striking outcome of this research involves the stability and quiet signal generation of newly designed TMBs, unlike natural ones, which may show variability in their readings and noise. These engineered nanopores have repeatedly and reliably delivered consistent performances, opening future applications ranging from portable DNA and RNA sequencing devices to highly specialized sensing tools at research and industrial levels.

Small Molecule Sensing: Expanding the Horizon Creating a new generation of nanopores that are able to detect small molecules, such as metabolites, is a big step in developing nanopores. That would revolutionize testing for metabolomic and diagnostic processes that now involves big and specialized machinery. A team from UW Medicine led by biochemistry professor David Baker achieved a huge leap towards that goal with the design of proteins capable of binding selectively tiny chemicals. These proteins were incorporated into TMB pores, thus allowing the observation of single-molecule binding events, which is hardly possible using typical nanopore technology.

Shaping the Future of Nanopore Technology 

Custom design of TMB pores is the transformative success of nanopore technology, opening new vistas in both research and diagnostics. Not only does such an advance extend the scope of portable sequencing devices, but such nanopores are envisioned to be highly specialized in the detection of diverse molecules. The great potential to perform biomolecular analysis right at one’s fingertips is indeed a groundbreaking fact that places the most advanced diagnostic tools within a reachable perspective.

While we transcend beyond the limitation of the protein structures that nature could provide us with – moving on to de novo design, we are close to experiencing a revolution in molecular analysis. With such potential for tailoring nanopores for specific applications, the limits placed on the development of science and technology would definitely be profound.

Know more about TMB Pores here.