Kinase sensor

1/21/2013

Nanoengineering permits the manufacturing of sensors of unprecedented accuracy to detect biomolecules at very low concentrations as they arise, for example, as signals in living cells. In an important type of cellular signaling, proteins are modified through addition of a phosphate group by other proteins, so-called kinases. Kinases are involved in various types of cancers; therefore, bioengineers led by Logan Liu of University of Illinois seek to develop a nanosensor to detect kinase activity. As described in a recent report published in ACS Nano, they grafted short peptides, containing a tyrosine amino acid, on nanometer scale gold surfaces. Phosphate groups are negatively charged, and as the groups are transferred from the kinases to the peptide’s tyrosine, the overall charge of the grafted peptides increase. Bioengineers detected then the phosphorylated peptides by applying electrical fields that would drive the charged phosphate group towards the surface or away from it, depending on the voltage polarity; the resulting conformational change of peptides can be recognized by shining light on the nanosensors as optical properties of molecules near metal surfaces are amplified. In order to make the nanodevice really work, the bioengineers needed to optimize the peptide sequence, know how phosphorylation and voltages alter the near-surface conformation of the peptides and how to interpret the measured optical signals. In other words, they needed a microscopic view of the nanodevice! Such view was achieved through molecular dynamics simulations by the Schulten group of CPLC. The combination of nanoengineering and molecular dynamics simulations produced indeed a satisfactory kinase sensor prototype. For more information, visit our kinase sensor website.