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Eight identical peptides created holes of two sizes, and the mixed shapes of disease proteins were sorted out using electric current.
Researchers from India and Germany published results showing that eight identical short peptides self-assemble into two states, small and large, in the membrane, and that the shapes of sugars, peptides, and disease-related proteins can be distinguished based on the traces of electric current of the molecules passing through them. In vitro, the large pores distinguished alpha-synuclein variants associated with Parkinson’s disease and different aggregation stages.
This does not mean that we can now diagnose Parkinson’s disease or Lou Gehrig’s disease with a single drop of blood. This is a single molecule experiment conducted on purified proteins and artificial lipid membranes, and the complex components of real blood, false detection rate, repeatability, and ability to distinguish between patients have not been verified.
How did the hole create itself?
Eight pPorA peptides of 40 amino acids came together to create a helical passage that penetrated the membrane. The same octamer showed a small state of 2.4 nanosiemens and a large state of 3.5 nanosiemens at similar frequencies under the condition of 1 mol potassium chloride. The shape and stability were also controlled by changing the amino acid at a specific position.
What did you distinguish?
There was a difference in that large sugars adhered to small holes but did not pass through them, whereas they did pass through large holes. Large pores differentiated several alpha-synuclein variants and monomeric, oligomeric, and fibrillar stages by the magnitude and duration of current blockage. The small pore detected humanin and SOD1-related small peptides.
What does 20 nanomole mean?
The paper reported a binding affinity of approximately 20 nanomolar to the C-terminal deletion alpha-synuclein variant associated with Parkinson’s disease. This indicates how well the pore and protein interacted under purification conditions. It is not a percentage of patients’ blood that does not miss disease or an accuracy number that accurately identifies healthy people.
Why are both sizes useful?
If the channel has only one fixed size, proteins of different shapes will be read in only one way. If the same components make both diameters, the signal can be split to accommodate large proteins and small peptides. However, molecular dynamics calculations have limitations in that they use simplified passages and high electric fields.
What is the next verification?
Selectivity, long-term stability of the membrane, and manufacturing variations must be tested in physiological salts and real body fluids. Only after screening various patient groups and disclosing the sensitivity and specificity can the possibility of diagnosis be stated. The value of this step lies in creating a sensing platform called the flexible helical peptide pore.
Primary sources and independent checks
Nature Nanotechnology original paper