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Nonequilibrium Capture Rates Induce Protein Accumulation and Enhanced Adsorption to Solid-State Nanopores

Freedman, Kevin J. (author)
Haq, Syed Raza (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Fletcher, Michael R. (author)
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Foley, Joe P. (author)
Jemth, Per (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Edel, Joshua B. (author)
Kim, Min Jun (author)
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 (creator_code:org_t)
2014-11-26
2014
English.
In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 8:12, s. 12238-12249
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Single molecule capturing of analytes using an electrically biased nanopore is the fundamental mechanism in which nearly all nanopore experiments are conducted. With pore dimensions being on the order of a single molecule, the spatial zone of sensing only contains approximately a zeptoliter of volume. As a result, nanopores offer high precision sensing within the pore but provide little to no information about the analytes outside the pore. In this study, we use capture frequency and rate balance theory to predict and study the accumulation of proteins at the entrance to the pore. Protein accumulation is found to have positive attributes such as capture rate enhancement over time but can additionally lead to negative effects such as long-term blockages typically attributed to protein adsorption on the surface of the pore. Working with the folded and unfolded states of the protein domain PDZ2 from SAP97, we show that applying short (e.g., 3-25 s in duration) positive voltage pulses, rather than a constant voltage, can prevent long-term current blockades (i.e., adsorption events). By showing that the concentration of proteins around the pore can be controlled in real time using modified voltage protocols, new experiments can be explored which study the role of concentration on single molecular kinetics including protein aggregation, folding, and protein binding.

Subject headings

TEKNIK OCH TEKNOLOGIER  -- Nanoteknik (hsv//swe)
ENGINEERING AND TECHNOLOGY  -- Nano-technology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

Keyword

nanopores
capture rate
protein adsorption
biosensors
protein kinetics
energy barrier

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ref (subject category)
art (subject category)

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