Sensing Native and Unfolded Single Protein Molecules with Solid-State Nanopores

The translocation of biological molecules through a solid-state nanopore device allows the experimenter to measure the size and conformation of individual biomolecules as they pass through the nanopore. The size and conformation of individual biomolecules can be measured by the amplitude and time duration of the current blockage pulses produced when the biomolecules pass through a nanopore in an ionic solution. The time duration is inversely proportional to the charge density of a uniformly charged linear biomolecule such as a DNA or the total charge of a globular shaped protein molecule. In this thesis, a linear repeat protein, CTPR series, was chosen for studying how a heterogeneously charged protein in its unfolded state or linear form passing through a nanopore affects the translocation time. It has been observed in these protein translocation experiments that the time to transit through the pore depends on the local net charge of an unfolded protein more than the total charge. Modeling by a Langevin equation reveals the effects of inhomogeneous charge on translocation time. This insight into translocation kinetics may allow for the more accurate determination of protein properties based on the electrical signals arising from nanopore measurements.