Probing protein nanopores with poly(ethylene glycol)s
Wenxing Liu
Department of Biology, The Catholic University of America, Washington, DC, USA
Search for more papers by this authorCorresponding Author
Ekaterina M. Nestorovich
Department of Biology, The Catholic University of America, Washington, DC, USA
Correspondence
Ekaterina M. Nestorovich, Department of Biology, The Catholic University of America, 620 Michigan Ave, WA DC, 20064, USA.
Email: [email protected]
Search for more papers by this authorWenxing Liu
Department of Biology, The Catholic University of America, Washington, DC, USA
Search for more papers by this authorCorresponding Author
Ekaterina M. Nestorovich
Department of Biology, The Catholic University of America, Washington, DC, USA
Correspondence
Ekaterina M. Nestorovich, Department of Biology, The Catholic University of America, 620 Michigan Ave, WA DC, 20064, USA.
Email: [email protected]
Search for more papers by this authorAbstract
Neutral water-soluble poly(ethylene glycol)s (PEGs) have been extensively explored in protein nanopore research for the past several decades. The principal use of PEGs is to investigate the membrane protein ion channel physical characteristics and transport properties. In addition, protein nanopores are used to study polymer–protein interactions and polymer physicochemical properties. In this review, we focus on the biophysical studies on probing protein ion channels with PEGs, specifically on nanopore sizing by PEG partitioning. We discuss the fluctuation analysis of ion channel currents in response to the PEGs moving within their confined geometries. The advantages, limitations, and recent developments of the approach are also addressed.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this review article as no new data were created or analyzed in this study.
REFERENCES
- 1Montal, M., & Mueller, P. (1972). Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proceedings of the National Academy of Sciences of the United States of America, 69, 3561–3566.
- 2Krasilnikov, O. V., Sabirov, R. Z., Ternovsky, V. I., Merzliak, P. G., & Tashmukhamedov, B. A. (1988). The structure of Staphylococcus aureus alpha-toxin-induced ionic channel. General Physiology and Biophysics, 7, 467–473.
- 3Krasilnikov, O. V., Sabirov, R. Z., Ternovsky, V. I., Merzliak, P. G., & Muratkhodjaev, J. N. (1992). A simple method for the determination of the pore radius of ion channels in planar lipid bilayer membranes. FEMS Microbiology Immunology, 5, 93–100.
- 4Kuga, S. (1981). Pore size distribution analysis of gel substances by size exclusion chromatography. Journal of Chromatography A, 206, 449–461.
- 5Bezrukov, S. M., Vodyanoy, I., & Parsegian, V. A. (1994). Counting polymers moving through a single ion channel. Nature, 370, 279–281.
- 6Parsegian, V. A., Bezrukov, S. M., & Vodyanoy, I. (1995). Watching small molecules move: Interrogating ionic channels using neutral solutes. Bioscience Reports, 15, 503–514.
- 7Bezrukov, S. M., Vodyanoy, I., Brutyan, R. A., & Kasianowicz, J. J. (1996). Dynamics and free energy of polymers partitioning into a nanoscale pore. Macromolecules, 29, 8517–8522.
- 8Krasilnikov, O. V., Rodrigues, C. G., & Bezrukov, S. M. (2006). Single polymer molecules in a protein nanopore in the limit of a strong polymer-pore attraction. Physical Review Letter, 97, 018301.
- 9Rodrigues, C. G., Machado, D. C., Chevtchenko, S. F., & Krasilnikov, O. V. (2008). Mechanism of KCl enhancement in detection of nonionic polymers by nanopore sensors. Biophysical Journal, 95, 5186–5192.
- 10Rodrigues, C. G., Machado, D. C., Da Silva, A. M. B., Júnior, J. J. S., & Krasilnikov, O. V. (2011). Hofmeister effect in confined spaces: Halogen ions and single molecule detection. Biophysical Journal, 100, 2929–2935.
- 11Baaken, G., Halimeh, I., Bacri, L., Pelta, J., Oukhaled, A., & Behrends, J. C. (2015). High-resolution size-discrimination of single nonionic synthetic polymers with a highly charged biological nanopore. ACS Nano, 9, 6443–6449.
- 12Robertson, J. W. F., Rodrigues, C. G., Stanford, V. M., Rubinson, K. A., Krasilnikov, O. V., & Kasianowicz, J. J. (2007). Single-molecule mass spectrometry in solution using a solitary nanopore. Proceedings of the National Academy of Sciences of the United States of America, 104, 8207–8211.
- 13Bezrukov, S. M., & Kasianowicz, J. J. (1993). Current noise reveals protonation kinetics and number of ionizable sites in an open protein ion channel. Physical Review Letter, 70, 2352–2355.
- 14Kasianowicz, J. J., Brandin, E., Branton, D., & Deamer, D. W. (1996). Characterization of individual polynucleotide molecules using a membrane channel. Proceedings of the National Academy of Sciences of the United States of America, 93, 13770–13773.
- 15Rostovtseva, T. K., & Bezrukov, S. M. (1998). ATP transport through a single mitochondrial channel, VDAC, studied by current fluctuation analysis. Biophysical Journal, 74, 2365–2373.
- 16Kasianowicz, J. J., Balijepalli, A. K., Ettedgui, J., Forstater, J. H., Wang, H., Zhang, H., & Robertson, J. W. (2015). Analytical applications for pore-forming proteins. Biochimica et Biophysica Acta, 1858(3), 593–606.
- 17Robertson, J. W. F., Ghimire, M. L., & Reiner, J. E. (2021). Nanopore sensing: A physical-chemical approach. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1863, 183644.
- 18Krasilnikov, O. V. (2002). In J. J. Kasianowicz, M. S. Z. Kellermayer, & D. W. Deamer (Eds.), Structure and Dynamics of Confined Polymers (pp. 97–115). Springer.
10.1007/978-94-010-0401-5_6 Google Scholar
- 19Merzlyak, P. G., Yuldasheva, L. N., Rodrigues, C. G., Carneiro, C. M. M., Krasilnikov, O. V., & Bezrukov, S. M. (1999). Polymeric nonelectrolytes to probe pore geometry: Application to the alpha-toxin transmembrane channel. Biophysical Journal, 77, 3023–3033.
- 20Zalipsky, S., & Harris, J. M. (1997). Poly(ethylene glycol) (pp. 1–13). American Chemical Society.
- 21Knop, K., Hoogenboom, R., Fischer, D., & Schubert, U. S. (2010). Poly(ethylene glycol) in drug delivery: Pros and cons as well as potential alternatives. Angewandte Chemie International Edition, 49, 6288–6308.
- 22D'souza, A. A., & Shegokar, R. (2016). Polyethylene glycol (PEG): A versatile polymer for pharmaceutical applications. Expert Opinion on Drug Delivery, 13, 1257–1275.
- 23Harris, J. M. (2013). Poly(ethylene glycol) Chemistry: Biotechnical and Biomedical Applications. New York, Springer Science and Business Media, LLC.
- 24Herold, D. A., Keil, K., & Bruns, D. E. (1989). Oxidation of polyethylene glycols by alcohol dehydrogenase. Biochemical Pharmacology, 38, 73–76.
- 25Bailey Jr, E. F., & Callard, R. W. (1959). Some properties of poly(ethylene oxide)1 in aqueous solution. Journal of Applied Polymer Science, 1, 56–62.
10.1002/app.1959.070010110 Google Scholar
- 26Israelachvili, J. (1997). The different faces of poly(ethylene glycol). Proceedings of the National Academy of Sciences of the United States of America, 94, 8378–8379.
- 27Özdemir, C., & Güner, A. (2006). Solution thermodynamics of poly(ethylene glycol)/water systems. Journal of Applied Polymer Science, 101, 203–216.
- 28Malcolm, G. N., & Rowlinson, J. S. (1957). The thermodynamic properties of aqueous solutions of polyethylene glycol, polypropylene glycol and dioxane. Transactions of the Faraday Society, 53, 921–931.
- 29Saeki, S., Kuwahara, N., Nakata, M., & Kaneko, M. (1977). Phase separation of poly(ethylene glycol)-water-salt systems. Polymer, 18, 1027–1031.
- 30Aseyev, V., Tenhu, H., & Winnik, F. M. (2011). In A. H. E. Müller, & O. Borisov (Eds.), Self Organized Nanostructures of Amphiphilic Block Copolymers II (pp. 29–89). Springer Berlin Heidelberg.
- 31De Gennes, P. G. (1975). Collapse of a polymer chain in poor solvents. Journal De Physique Letters, 36, 55–57.
10.1051/jphyslet:0197500360305500 Google Scholar
- 32De Gennes, P. G. (1978). Collapse of a flexible polymer chain II. Journal De Physique Letters, 39, 299–301.
- 33Odagiri, K., & Seki, K. (2015). Coil–globule transition of a polymer involved in excluded-volume interactions with macromolecules. Journal of Chemical Physics, 143, 134903.
- 34Kjellander, R., & Florin, E. (1981). Water structure and changes in thermal stability of the system poly(ethylene oxide)–water. Journal of the Chemical Society, Faraday Transactions 1, 77, 2053–2077.
- 35Karlström, G., & Engkvist, O. (1997). Poly(ethylene glycol) (pp. 16–30). American Chemical Society.
10.1021/bk-1997-0680.ch002 Google Scholar
- 36Nichols, M. D., Scott, E. A., & Elbert, D. L. (2009). Factors affecting size and swelling of poly(ethylene glycol) microspheres formed in aqueous sodium sulfate solutions without surfactants. Biomaterials, 30, 5283–5291.
- 37Piguet, F., Ouldali, H., Discala, F., Breton, M.-F., Behrends, J. C., Pelta, J., & Oukhaled, A. (2016). High temperature extends the range of size discrimination of nonionic polymers by a biological nanopore. Science Reports, 6, 38675.
- 38Venohr, H., Fraaije, V., Strunk, H., & Borchard, W. (1998). Static and dynamic light scattering from aqueous poly(ethylene oxide) solutions. European Polymer Journal, 34, 723–732.
- 39Hey, M. J., Jackson, D. P., & Yan, H. (2005). The salting-out effect and phase separation in aqueous solutions of electrolytes and poly(ethylene glycol). Polymer, 46, 2567–2572.
- 40Heeb, R., Lee, S., Venkataraman, N. V., & Spencer, N. D. (2009). Influence of salt on the aqueous lubrication properties of end-grafted, ethylene glycol-based self-assembled monolayers. ACS Applied Materials & Interfaces, 1, 1105–1112.
- 41Brunchi, C.-E., & Ghimici, L. (2012). PEG in aqueous salt solution. Viscosity and separation ability in a TiO2 suspension. Revue Roumaine de Chimie, 58, 183–188.
- 42Sadeghi, R., & Jahani, F. (2012). Salting-in and salting-out of water-soluble polymers in aqueous salt solutions. Journal of Physical Chemistry B, 116, 5234–5241.
- 43Kuhn, H., Försterling, H.-D., & Waldeck, D. H. (2009). Principles of Physical Chemistry, 2nd Edition. John Wiley & Sons.
- 44Couper, A., & Stepto, R. F. T. (1969). Diffusion of low-molecular weight poly(ethylene oxide) in water. Transactions of the Faraday Society, 65, 2486–2496.
- 45Berezhkovskii, A. M., Bezrukov, S. M., Bicout, D. J., & Weiss, G. H. (1999). The influence of polymer on the diffusion of a spherical tracer. Journal of Chemical Physics, 111, 5641–5644.
- 46Bezrukov, S. M., & Vodyanoy, I. (1993). Probing alamethicin channels with water-soluble polymers. Effect on conductance of channel states. Biophysical Journal, 64, 16–25.
- 47Stojilkovic, K. S., Berezhkovskii, A. M., Zitserman, V. Y., & Bezrukov, S. M. (2003). Conductivity and microviscosity of electrolyte solutions containing polyethylene glycols. Journal of Chemical Physics, 119, 6973–6978.
- 48Marcus, Y. (1997). Ion Properties. CRC Press.
- 49Robinson, R. A., & Stokes, R. H. (1965). Electrolyte Solutions; the Measurement and Interpretation of Conductance, Chemical Potential, and Diffusion in Solutions of Simple Electrolytes. Butterworths.
- 50Zitserman, V. Y., Stojilkovich, K. S., Berezhkovskii, A. M., & Bezrukov, S. M. (2005). Electrical conductivity of aqueous solutions of polyethylene glycol. Russian Journal of Physical Chemistry, 79, 1083–1089.
- 51Colombini, M. (1980). Pore size and properties of channels from mitochondria isolated from Neurospora crassa. The Journal of Membrane Biology, 53, 79–84.
- 52Zimmerberg, J., & Parsegian, V. A. (1986). Polymer inaccessible volume changes during opening and closing of a voltage-dependent ionic channel. Nature, 323, 36–39.
- 53Zimmerberg, J., & Parsegian, V. A. (1987). Water movement during channel opening and closing. Journal of Bioenergetics and Biomembranes, 19, 351–358.
- 54Queralt-Martín, M., Hoogerheide, D. P., Noskov, S. Y., Berezhkovskii, A. M., Rostovtseva, T. K., & Bezrukov, S. M. (2020). VDAC gating thermodynamics, but not gating kinetics, are virtually temperature independent. Biophysical Journal, 119, 2584–2592.
- 55Vodyanoy, I., & Bezrukov, S. M. (1992). Sizing of an ion pore by access resistance measurements. Biophysical Journal, 62, 10–11.
- 56Bezrukov, S. M. (2000). Ion channels as molecular coulter counters to probe metabolite transport. The Journal of Membrane Biology, 174, 1–13.
- 57Mark, J. E., & Flory, P. J. (1965). The configuration of the polyoxyethylene chain. Journal of the American Chemical Society, 87, 1415–1423.
- 58Foster, K. R., Cheever, E., Leonard, J. B., & Blum, F. D. (1984). Transport properties of polymer solutions. A comparative approach. Biophysical Journal, 45, 975–984.
- 59Bordi, F., Cametti, C., & Di Biasio, A. (1988). Electrical conductivity behavior of poly(ethylene oxide) in aqueous electrolyte solutions. Journal of Physical Chemistry, 92, 4772–4777.
- 60Sabirov, R. Z., Krasilnikov, O. V., Ternovsky, V. I., & Merzliak, P. G. (1993). Relation between ionic channel conductance and conductivity of media containing different nonelectrolytes. A novel method of pore size determination. General Physiology and Biophysics, 12, 95–111.
- 61Rostovtseva, T. K., Nestorovich, E. M., Bezrukov, S. M. (2002). Partitioning of differently sized poly(ethylene glycol)s into OmpF porin. Biophysical Journal, 82, 160–169.
- 62Casassa, E. F. (1967). Equilibrium distribution of flexible polymer chains between a macroscopic solution phase and small voids. Journal of Polymer Science Part B: Polymer Letters, 5, 773–778.
- 63Colton, C. K., Satterfield, C. N., & Lai, C.-J. (1975). Diffusion and partitioning of macromolecules within finely porous glass. AIChE Journal, 21, 289–298.
- 64Gennes, P.-G. D. (1979). Scaling Concepts in Polymer Physics. Cornell University Press.
- 65Grosberg, A. J., & Chochlov, A. R. (1994). Statistical Physics of Macromolecules. AIP Press.
- 66Bezrukov, S. M., & Kasianowicz, J. J. (2002). In J. J. Kasianowicz, M. S. Z. Kellermayer, & D. W. Deamer (Eds.), Structure and Dynamics of Confined Polymers (pp. 117–130). Springer.
10.1007/978-94-010-0401-5_7 Google Scholar
- 67Carneiro, C. M. M., Krasilnikov, O. V., Yuldasheva, L. N., Campos De Carvalho, A. C., & Nogueira, R. A. (1997). Is the mammalian porin channel, VDAC, a perfect cylinder in the high conductance state? FEBS Letters, 416, 187–189.
- 68Nestorovich, E. M., Karginov, V. A., & Bezrukov, S. M. (2010). Polymer partitioning and ion selectivity suggest asymmetrical shape for the membrane pore formed by epsilon toxin. Biophysical Journal, 99, 782–789.
- 69Krasilnikov, J. B., Da Cru, O. V., & Nogueira, R. A. (1998). A novel approach to study the geometry of the water lumen of ion channels: Colicin Ia channels in planar lipid bilayers. Journal of Membrane Biology, 161, 83–92.
- 70Yuldasheva, L. N., Merzlyak, P. G., Zitzer, A. O., Rodrigues, C. G., Bhakdi, S., & Krasilnikov, O. V. (2001). Lumen geometry of ion channels formed by Vibrio cholerae EL Tor cytolysin elucidated by nonelectrolyte exclusion. Biochimica Et Biophysica Acta, 1512, 53–63.
- 71Carneiro, C. M. M., Merzlyak, P. G., Yuldasheva, L. N., Silva, L. G., Thinnes, F. P., & Krasilnikov, O. V. (2003). Probing the volume changes during voltage gating of Porin 31BM channel with nonelectrolyte polymers. Biochimica Et Biophysica Acta, 1612, 144–153.
- 72Ostroumova, O. S., Gurnev, P. A., & Schagina, L. V., & Bezrukov, S. M. (2007). Asymmetry of syringomycin E channel studied by polymer partitioning. FEBS Letters, 581, 804–808.
- 73Niedzwiecki, D. J., Mohammad, M. M., & Movileanu, L. (2012). Inspection of the engineered FhuA ΔC/Δ4L protein nanopore by polymer exclusion. Biophysical Journal, 103, 2115–2124.
- 74Krasilnikov, O. V., Sabirov, R. Z., & Okada, Y. (2011). ATP hydrolysis-dependent asymmetry of the conformation of CFTR channel pore. The Journal of Physiological Sciences, 61, 267–278.
- 75Sabirov, R. Z., & Okada, Y. (2004). Wide nanoscopic pore of maxi-anion channel suits its function as an ATP-conductive pathway. Biophysical Journal, 87, 1672–1685.
- 76Vodyanoy, I., Bezrukov, S. M., & Parsegian, V. A. (1993). Probing alamethicin channels with water-soluble polymers. Size-modulated osmotic action. Biophysical Journal, 65, 2097–2105.
- 77Kasianowicz, J. J., & Bezrukov, S. M. (1995). Protonation dynamics of the alpha-toxin ion channel from spectral analysis of pH-dependent current fluctuations. Biophysical Journal, 69, 94–105.
- 78Song, L., Hobaugh, M. R., Shustak, C., Cheley, S., Bayley, H., & Gouaux, J. E. (1996). Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science (New York, NY), 274, 1859–1865.
- 79Krasilnikov, O. V., Ternovsky, V. I., Musaev, Y. M., & Tashmukhamedov, B. A. (1980). Influence of staphylotoxin on conductance of bilayer phospholipid membranes. Doklady Akademii Nauk SSSR, 7, 66–68.
- 80Krasil'nikov, O. V., Ternovskiĭ, V. I., & Tashmukhamedov, B. A. (1981). Properties of conductivity channels induced in phospholipid bilayer membranes by alpha-staphylotoxin. Biofizika, 26, 271–276.
- 81Krasilnikov, O. V., Merzliak, P. G., Sabirov, R. Z., & Tashmuk-Hamedov, B. A. (1990). Memory is a property of an ion channels pool: Ion channels formed by Staphylococcus aureus alpha-toxin. General Physiology and Biophysics, 9, 569–575.
- 82Menestrina, G. (1986). Ionic channels formed by Staphylococcus aureus alpha-toxin: Voltage-dependent inhibition by divalent and trivalent cations. Journal of Membrane Biology, 90, 177–190.
- 83Sabirov, R. Z. (1991). Influence of some nonelectrolytes on conductance of bulk solution and conductivity of ion channel-determination of pore radius from electric measurements. Biological Membranes, 8, 280–291.
- 84Movileanu, L., Cheley, S., Howorka, S., Braha, O., & Bayley, H. (2001). Location of a constriction in the lumen of a transmembrane pore by targeted covalent attachment of polymer molecules. Journal of General Physiology, 117, 239–252.
- 85Bezrukov, S. M., & Kasianowicz, J. J. (1997). The charge state of an ion channel controls neutral polymer entry into its pore. European Biophysics Journal, 26, 471–476.
- 86Aguilella-Arzo, M., & Aguilella, V. M. (2021). PEG Equilibrium Partitioning in the α-Hemolysin Channel: Neutral Polymer Interaction with Channel Charges. Biomacromolecules, 22, 410–418.
- 87Wu, J., Zhao, C., Lin, W., Hu, R., Wang, Q., Chen, H., Li, L., Chen, S., & Zheng, J. (2014). Binding characteristics between polyethylene glycol (PEG) and proteins in aqueous solution. Journal of Materials Chemistry B, 2, 2983–2992.
- 88Kasianowicz, J. J., Robertson, J. W. F., Chan, E. R., Reiner, J. E., & Stanford, V. M. (2008). Nanoscopic porous sensors. Annual Review of Analytical Chemistry, 1, 737–766.
- 89Reiner, J. E., Kasianowicz, J. J., Nablo, B. J., & Robertson, J. W. F. (2010). Theory for polymer analysis using nanopore-based single-molecule mass spectrometry. Proceedings of the National Academy of Sciences of the United States of America, 107, 12080–12085.
- 90Bailey, F. E., & Koleske, J. V. (1976). Poly(ethylene oxide). Academic Press.
- 91Bailey, F. E., & Koleske, J. V. (1991). Alkylene Oxides and Their Polymers. Marcel Dekker Inc.
- 92Balijepalli, A., Robertson, J. W. F., Reiner, J. E., Kasianowicz, J. J., & Pastor, R. W. (2013). Theory of polymer–nanopore interactions refined using molecular dynamics simulations. Journal of the American Chemical Society, 135, 7064–7072.
- 93Wang, H., Kasianowicz, J. J., Robertson, J. W. F., Poster, D. L., & Ettedgui, J. (2019). A comparison of ion channel current blockades caused by individual poly(ethylene glycol) molecules and polyoxometalate nanoclusters. European Physical Journal E: Soft Matter, 42, 83.
- 94Breton, M. F., Discala, F., Bacri, L., Foster, D., Pelta, J., & Oukhaled, A. (2013). Exploration of neutral versus polyelectrolyte behavior of poly(ethylene glycol)s in alkali ion solutions using single-nanopore recording. Journal of Physical Chemistry Letters, 4, 2202–2208.
- 95Boukhet, M., Piguet, F., Ouldali, H., Pastoriza-Gallego, M., Pelta, J., & Oukhaled, A. (2016). Probing driving forces in aerolysin and α-hemolysin biological nanopores: Electrophoresis versus electroosmosis. Nanoscale, 8, 18352–18359.
- 96Poudel, L., Podgornik, R., & Ching, W.-Y. (2017). The hydration effect and selectivity of alkali metal ions on poly(ethylene glycol) models in cyclic and linear topology. Journal of Physical Chemistry A, 121, 4721–4731.
- 97Angevine, C. E., Chavis, A. E., Kothalawala, N., Dass, A., & Reiner, J. E. (2014). Enhanced single molecule mass spectrometry via charged metallic clusters. Analytical Chemistry, 86, 11077–11085.
- 98Angevine, C. E., Robertson, J. W. F., Dass, A., & Reiner, J. E. (2021). Laser-based temperature control to study the roles of entropy and enthalpy in polymer-nanopore interactions. Science Advances, 7, eabf5462.
- 99Movileanu, L., Cheley, S., & Bayley, H. (2003). Partitioning of individual flexible polymers into a nanoscopic protein pore. Biophysical Journal, 85, 897–910.
- 100Daoud, M., & De Gennes, P. G. (1977). Statistics of macromolecular solutions trapped in small pores. Journal de Physique, 38, 85–93.
- 101Howorka, S., Movileanu, L., Lu, X., Magnon, M., Cheley, S., Braha, O., & Bayley, H. (2000). A protein pore with a single polymer chain tethered within the lumen. Journal of the American Chemical Society, 122, 2411–2416.
- 102Movileanu, L., Howorka, S., Braha, O., & Bayley, H. (2000). Detecting protein analytes that modulate transmembrane movement of a polymer chain within a single protein pore. Nature Biotechnology, 18, 1091–1095.
- 103Movileanu, L., & Bayley, H. (2001). Partitioning of a polymer into a nanoscopic protein pore obeys a simple scaling law. Proceedings of the National Academy of Sciences of the United States of America, 98, 10137–10141.
- 104Krasilnikov, O. V., & Bezrukov, S. M. (2004). Polymer partitioning from nonideal solutions into protein voids. Macromolecules, 37, 2650–2657.
- 105Oukhaled, A. G., Biance, A.-L., Pelta, J., Auvray, L., & Bacri, L. (2012). Transport of long neutral polymers in the semidilute regime through a protein nanopore. Physical Review Letter, 108, 088104.
- 106Cifra, P., & Teraoka, I. (2002). Partitioning of polymer chains in solution with a square channel: Lattice Monte Carlo simulations. Polymer, 43, 2409–2415.
- 107Hermsen, G. F., De Geeter, B. A., Van Der Vegt, N. F. A., & Wessling, M. (2002). Monte Carlo simulation of partially confined flexible polymers. Macromolecules, 35, 5267–5272.
- 108Zitserman, V. Y., Berezhkovskii, A. M., Parsegian, V. A., & Bezrukov, S. M. (2005). Nonideality of polymer solutions in the pore and concentration-dependent partitioning. Journal of Chemical Physics, 123, 146101.
- 109Alcaraz, A., López, M. L., Queralt-Martín, M., & Aguilella, V. M. (2017). Ion transport in confined geometries below the nanoscale: Access resistance dominates protein channel conductance in diluted solutions. ACS Nano, 11, 10392–10400.
- 110Muthukumar, M. (2016). Polymer Translocation. CRC Press.
10.1201/b10901 Google Scholar
- 111Zhou, H.-X., Rivas, G., & Minton, A. P. (2008). Macromolecular crowding and confinement: Biochemical, biophysical, and potential physiological consequences. Annual Review of Biophysics, 37, 375–397.
- 112Podgornik, R., Hopkins, J., Parsegian, V. A., & Muthukumar, M. (2012). Polymers pushing polymers: Polymer mixtures in thermodynamic equilibrium with a pore. Macromolecules, 45, 8921–8928.
- 113Aksoyoglu, M. A, Podgornik, R., Bezrukov, S. M., Gurnev, P. A., Muthukumar, M., & Parsegian, V. A. (2016). Size-dependent forced PEG partitioning into channels: VDAC, OmpC, and α-hemolysin. Proceedings of the National Academy of Sciences of the United States of America, 113, 9003–9008.
- 114Gurnev, P. A., Stanley, C. B., Aksoyoglu, M. A., Hong, K., Parsegian, V. A., & Bezrukov, S. M. (2017). Poly(ethylene glycol)s in semidilute regime: Radius of gyration in the bulk and partitioning into a nanopore. Macromolecules, 50, 2477–2483.
- 115Larimi, M. G., Mayse, L. A., & Movileanu, L. (2019). Interactions of a polypeptide with a protein nanopore under crowding conditions. ACS Nano, 13, 4469–4477.
- 116Wolfe, J. T., Krantz, B. A., Rainey, G. J. A., & Young, J. A. T., & Collier, R. J. (2005). Whole-cell voltage clamp measurements of anthrax toxin pore current. Journal of Biological Chemistry, 280, 39417–39422.
- 117Nablo, B. J., Halverson, K. M., Robertson, J. W. F., Nguyen, T. L., Panchal, R. G., Gussio, R., Bavari, S., Krasilnikov, O. V., & Kasianowicz, J. J. (2008). Sizing the Bacillus anthracis PA63 channel with nonelectrolyte poly(ethylene glycols). Biophysical Journal, 95, 1157–1164.
- 118Moayeri, M., Leppla, S. H., Vrentas, C., Pomerantsev, A. P., & Liu, S. (2015). Anthrax pathogenesis. Annual Review of Microbiology, 69, 185–208.
- 119Krantz, B. A. (2015). In A. H. Delcour (Ed.), Electrophysiology of Unconventional Channels and Pores (pp. 209–240). Springer International Publishing.
10.1007/978-3-319-20149-8_9 Google Scholar
- 120Jiang, J., Pentelute, B. L., Collier, R. J., & Zhou, Z. H. (2015). Atomic structure of anthrax protective antigen pore elucidates toxin translocation. Nature, 521, 545–549.
- 121Blaustein, R. O., & Finkelstein, A. (1990). Diffusion limitation in the block by symmetric tetraalkylammonium ions of anthrax toxin channels in planar phospholipid bilayer membranes. Journal of General Physiology, 96, 943–957.
- 122Blaustein, R. O., & Finkelstein, A. (1990). Voltage-dependent block of anthrax toxin channels in planar phospholipid bilayer membranes by symmetric tetraalkylammonium ions. Effects on macroscopic conductance. Journal of General Physiology, 96, 905–919.
- 123Bárcena-Uribarri, I., Thein, M., Maier, E., Bonde, M., Bergström, S., & Benz, R. (2013). Use of nonelectrolytes reveals the channel size and oligomeric constitution of the Borrelia burgdorferi P66 porin. PLoS One, 8, e78272.
- 124Jessberger, N., Dietrich, R., Schauer, K., Schwemmer, S., Märtlbauer, E., & Benz, R. (2020). Characteristics of the protein complexes and pores formed by Bacillus cereus hemolysin BL. Toxins (Basel), 12, 672.
- 125Dietrich, R., Jessberger, N., Ehling-Schulz, M., Märtlbauer, E., & Granum, P. E. (2021). The food poisoning toxins of Bacillus cereus. Toxins (Basel), 13, 98.
- 126Nestorovich, E. M., Sugawara, E., Nikaido, H., & Bezrukov, S M. (2006). Pseudomonas aeruginosa porin OprF: Properties of the channel. Journal of Biological Chemistry, 281, 16230–16237.
- 127Seifert, A., Göpfrich, K., Burns, J. R., Fertig, N., Keyser, U. F., & Howorka, S. (2015). Bilayer-spanning DNA nanopores with voltage-switching between open and closed state. ACS Nano, 9, 1117–1126.
- 128Tan, C. S., Riedl, J., Fleming, A. M., Burrows, C. J., & White, H. S. (2016). Kinetics of T3-DNA ligase-catalyzed phosphodiester bond formation measured using the α-hemolysin nanopore. ACS Nano, 10, 11127–11135.
- 129Lin, W.-C., & Licht, S. (2008). Polymer-based open-channel blockers for the acetylcholine receptor: The effect of spacer length on blockade kinetics. Biochemistry, 47, 9163–9173.
- 130Lin, W.-C., & Licht, S. (2014). Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor. PLoS One, 9, e112088.