Information and flux in a feedback controlled Brownian ratchet

We study a feedback control version of the flashing Brownian ratchet, in which the application of the flashing potential depends on the state of the particles to be controlled. Taking the view that the ratchet acts as a Maxwell's demon, we study the relationship that exists between the performance of the demon as a rectifier of random motion and the amount of information gathered by the demon through measurements. In the context of a simple measurement model, we derive analytic expressions for the flux induced by the feedback ratchet when acting on one particle and a few particles, and compare these results with those obtained with its open-loop version, which operates without information. Our main finding is that the flux in the feedback case has an upper bound proportional to the square-root of the information. Our results provide a quantitative analysis of the value of information in feedback ratchets, as well as an effective description of imperfect or noisy feedback ratchets that are relevant for experimental applications.Comment: LaTeX, 13 pages, 2 figure

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Cells are strongly out-of-equilibrium systems driven by continuous energy supply. They carry out many vital functions requiring active transport of various ingredients and organelles, some being small, others being large. The cytoskeleton, composed of three types of filaments, determines the shape of the cell and plays a role in cell motion. It also serves as a road network for the so-called cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated, in particular because its breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. We first review some biological facts obtained from experiments, and present some modeling attempts based on cellular automata. We start with background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the transportation of large cargos by multiple motors, we concentrate on axonal transport, because of its relevance for neuronal diseases. It is a challenge to understand how this transport is organized, given that it takes place in a confined environment and that several types of motors moving in opposite directions are involved. We review several features that could contribute to the efficiency of this transport, including the role of motor-motor interactions and of the dynamics of the underlying microtubule network. Finally, we discuss some still open questions.Comment: 74 pages, 43 figure

Is the Cell Really a Machine?

It has become customary to conceptualize the living cell as an intricate piece of machinery, different to a man-made machine only in terms of its superior complexity. This familiar understanding grounds the conviction that a cell's organization can be explained reductionistically, as well as the idea that its molecular pathways can be construed as deterministic circuits. The machine conception of the cell owes a great deal of its success to the methods traditionally used in molecular biology. However, the recent introduction of novel experimental techniques capable of tracking individual molecules within cells in real time is leading to the rapid accumulation of data that are inconsistent with an engineering view of the cell. This paper examines four major domains of current research in which the challenges to the machine conception of the cell are particularly pronounced: cellular architecture, protein complexes, intracellular transport, and cellular behaviour. It argues that a new theoretical understanding of the cell is emerging from the study of these phenomena which emphasizes the dynamic, self-organizing nature of its constitution, the fluidity and plasticity of its components, and the stochasticity and non-linearity of its underlying processes

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Mechano-chemical kinetics of DNA replication: identification of the translocation step of a replicative DNA polymerase

[EN] During DNA replication replicative polymerases move in discrete mechanical steps along the DNA template. To address how the chemical cycle is coupled to mechanical motion of the enzyme, here we use optical tweezers to study the translocation mechanism of individual bacteriophage Phi29 DNA polymerases during processive DNA replication. We determine the main kinetic parameters of the nucleotide incorporation cycle and their dependence on external load and nucleotide (dNTP) concentration. The data is inconsistent with power stroke models for translocation, instead supports a loose-coupling mechanism between chemical catalysis and mechanical translocation during DNA replication. According to this mechanism the DNA polymerase works by alternating between a dNTP/PPi-free state, which diffuses thermally between pre- and post-translocated states, and a dNTP/PPi-bound state where dNTP binding stabilizes the post-translocated state. We show how this thermal ratchet mechanism is used by the polymerase to generate work against large opposing loads (~50 pN).We thank Stephan Grill laboratory (MPI-CBG, Dresden) for help with data collection and E. Galburt, M. Manosas and M. De Vega for critical reading of the manuscript. Spanish Ministry of Economy and Competitiveness [BFU2011-29038 to J.L.C., BFU2013-44202 to J.M.V., BFU2011-23645 to M.S., FIS2010-17440, GR35/10-A920GR35/10-A-911 to F.J.C., MAT2013-49455-EXP to J.R.A.-G. and BFU2012-31825 to B.I.]; Regional Government of Madrid [S2009/MAT 1507 to J.L.C. and CDS2007-0015 to M.S.]; European Molecular Biology Organization [ASTF 276-2012 to J.M.L.]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [BFU2012-31825 to B.I.].Morin, J.; Cao, F.; Lázaro, J.; Arias-Gonzalez, JR.; Valpuesta, J.; Carrascosa, J.; Salas, M.... (2015). Mechano-chemical kinetics of DNA replication: identification of the translocation step of a replicative DNA polymerase. Nucleic Acids Research. 43(7):3643-3652. https://doi.org/10.1093/nar/gkv204S36433652437Steitz, T. A., & Steitz, J. A. (1993). A general two-metal-ion mechanism for catalytic RNA. Proceedings of the National Academy of Sciences, 90(14), 6498-6502. doi:10.1073/pnas.90.14.6498Nakamura, T., Zhao, Y., Yamagata, Y., Hua, Y., & Yang, W. (2012). Watching DNA polymerase η make a phosphodiester bond. Nature, 487(7406), 196-201. doi:10.1038/nature11181Kohlstaedt, L., Wang, J., Friedman, J., Rice, P., & Steitz, T. (1992). Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science, 256(5065), 1783-1790. doi:10.1126/science.1377403Steitz, T. A. (2006). Visualizing polynucleotide polymerase machines at work. The EMBO Journal, 25(15), 3458-3468. doi:10.1038/sj.emboj.7601211Zhang, H., Cao, W., Zakharova, E., Konigsberg, W., & De La Cruz, E. M. (2007). Fluorescence of 2-aminopurine reveals rapid conformational changes in the RB69 DNA polymerase-primer/template complexes upon binding and incorporation of matched deoxynucleoside triphosphates. Nucleic Acids Research, 35(18), 6052-6062. doi:10.1093/nar/gkm587Wang, W., Wu, E. Y., Hellinga, H. W., & Beese, L. S. (2012). Structural Factors That Determine Selectivity of a High Fidelity DNA Polymerase for Deoxy-, Dideoxy-, and Ribonucleotides. Journal of Biological Chemistry, 287(34), 28215-28226. doi:10.1074/jbc.m112.366609Berezhna, S. Y., Gill, J. P., Lamichhane, R., & Millar, D. P. (2012). Single-Molecule Förster Resonance Energy Transfer Reveals an Innate Fidelity Checkpoint in DNA Polymerase I. Journal of the American Chemical Society, 134(27), 11261-11268. doi:10.1021/ja3038273Hariharan, C., Bloom, L. B., Helquist, S. A., Kool, E. T., & Reha-Krantz, L. J. (2006). Dynamics of Nucleotide Incorporation:  Snapshots Revealed by 2-Aminopurine Fluorescence Studies†. Biochemistry, 45(9), 2836-2844. doi:10.1021/bi051644sJoyce, C. M., Potapova, O., DeLucia, A. M., Huang, X., Basu, V. P., & Grindley, N. D. F. (2008). Fingers-Closing and Other Rapid Conformational Changes in DNA Polymerase I (Klenow Fragment) and Their Role in Nucleotide Selectivity†. Biochemistry, 47(23), 6103-6116. doi:10.1021/bi7021848Vande Berg, B. J., Beard, W. A., & Wilson, S. H. (2000). DNA Structure and Aspartate 276 Influence Nucleotide Binding to Human DNA Polymerase β. Journal of Biological Chemistry, 276(5), 3408-3416. doi:10.1074/jbc.m002884200Showalter, A. K., & Tsai, M.-D. (2002). A Reexamination of the Nucleotide Incorporation Fidelity of DNA Polymerases†. Biochemistry, 41(34), 10571-10576. doi:10.1021/bi026021iShah, A. M., Li, S.-X., Anderson, K. S., & Sweasy, J. B. (2001). Y265H Mutator Mutant of DNA Polymerase β. Journal of Biological Chemistry, 276(14), 10824-10831. doi:10.1074/jbc.m008680200Rothwell, P. J., Mitaksov, V., & Waksman, G. (2005). Motions of the Fingers Subdomain of Klentaq1 Are Fast and Not Rate Limiting: Implications for the Molecular Basis of Fidelity in DNA Polymerases. Molecular Cell, 19(3), 345-355. doi:10.1016/j.molcel.2005.06.032Patel, S. S., Wong, I., & Johnson, K. A. (1991). Pre-steady-state kinetic analysis of processive DNA replication including complete characterization of an exonuclease-deficient mutant. Biochemistry, 30(2), 511-525. doi:10.1021/bi00216a029Luo, G., Wang, M., Konigsberg, W. H., & Xie, X. S. (2007). Single-molecule and ensemble fluorescence assays for a functionally important conformational change in T7 DNA polymerase. Proceedings of the National Academy of Sciences, 104(31), 12610-12615. doi:10.1073/pnas.0700920104Joyce, C. M., & Benkovic, S. J. (2004). DNA Polymerase Fidelity:  Kinetics, Structure, and Checkpoints†. Biochemistry, 43(45), 14317-14324. doi:10.1021/bi048422zFiala, K. A., & Suo, Z. (2004). Mechanism of DNA Polymerization Catalyzed bySulfolobus solfataricusP2 DNA Polymerase IV†. Biochemistry, 43(7), 2116-2125. doi:10.1021/bi035746zCramer, J., & Restle, T. (2005). Pre-steady-state Kinetic Characterization of the DinB Homologue DNA Polymerase ofSulfolobus solfataricus. Journal of Biological Chemistry, 280(49), 40552-40558. doi:10.1074/jbc.m504481200Choi, J.-Y., & Guengerich, F. P. (2005). Adduct Size Limits Efficient and Error-free Bypass Across Bulky N2-Guanine DNA Lesions by Human DNA Polymerase η. Journal of Molecular Biology, 352(1), 72-90. doi:10.1016/j.jmb.2005.06.079Olsen, T. J., Choi, Y., Sims, P. C., Gul, O. T., Corso, B. L., Dong, C., … Weiss, G. A. (2013). Electronic Measurements of Single-Molecule Processing by DNA Polymerase I (Klenow Fragment). Journal of the American Chemical Society, 135(21), 7855-7860. doi:10.1021/ja311603rAllen, W. J., Rothwell, P. J., & Waksman, G. (2008). An intramolecular FRET system monitors fingers subdomain opening in Klentaq1. Protein Science, 17(3), 401-408. doi:10.1110/ps.073309208Johnson, S. J., & Beese, L. S. (2004). Structures of Mismatch Replication Errors Observed in a DNA Polymerase. Cell, 116(6), 803-816. doi:10.1016/s0092-8674(04)00252-1Yin, Y. W., & Steitz, T. A. (2004). The Structural Mechanism of Translocation and Helicase Activity in T7 RNA Polymerase. Cell, 116(3), 393-404. doi:10.1016/s0092-8674(04)00120-5Golosov, A. A., Warren, J. J., Beese, L. S., & Karplus, M. (2010). The Mechanism of the Translocation Step in DNA Replication by DNA Polymerase I: A Computer Simulation Analysis. Structure, 18(1), 83-93. doi:10.1016/j.str.2009.10.014Zhang, C., & Burton, Z. F. (2004). Transcription Factors IIF and IIS and Nucleoside Triphosphate Substrates as Dynamic Probes of the Human RNA Polymerase II Mechanism. Journal of Molecular Biology, 342(4), 1085-1099. doi:10.1016/j.jmb.2004.07.070Nedialkov, Y. A., Gong, X. Q., Hovde, S. L., Yamaguchi, Y., Handa, H., Geiger, J. H., … Burton, Z. F. (2003). NTP-driven Translocation by Human RNA Polymerase II. Journal of Biological Chemistry, 278(20), 18303-18312. doi:10.1074/jbc.m301103200Gong, X. Q., Zhang, C., Feig, M., & Burton, Z. F. (2005). Dynamic Error Correction and Regulation of Downstream Bubble Opening by Human RNA Polymerase II. Molecular Cell, 18(4), 461-470. doi:10.1016/j.molcel.2005.04.011Guajardo, R., & Sousa, R. (1997). A model for the mechanism of polymerase translocation 1 1Edited by A. R. Fersht. Journal of Molecular Biology, 265(1), 8-19. doi:10.1006/jmbi.1996.0707Thomen, P., Lopez, P. J., & Heslot, F. (2005). Unravelling the Mechanism of RNA-Polymerase Forward Motion by Using Mechanical Force. Physical Review Letters, 94(12). doi:10.1103/physrevlett.94.128102Larson, M. H., Zhou, J., Kaplan, C. D., Palangat, M., Kornberg, R. D., Landick, R., & Block, S. M. (2012). Trigger loop dynamics mediate the balance between the transcriptional fidelity and speed of RNA polymerase II. Proceedings of the National Academy of Sciences, 109(17), 6555-6560. doi:10.1073/pnas.1200939109Bar-Nahum, G., Epshtein, V., Ruckenstein, A. E., Rafikov, R., Mustaev, A., & Nudler, E. (2005). A Ratchet Mechanism of Transcription Elongation and Its Control. Cell, 120(2), 183-193. doi:10.1016/j.cell.2004.11.045Bai, L., Fulbright, R. M., & Wang, M. D. (2007). Mechanochemical Kinetics of Transcription Elongation. Physical Review Letters, 98(6). doi:10.1103/physrevlett.98.068103Abbondanzieri, E. A., Greenleaf, W. J., Shaevitz, J. W., Landick, R., & Block, S. M. (2005). Direct observation of base-pair stepping by RNA polymerase. Nature, 438(7067), 460-465. doi:10.1038/nature04268Dangkulwanich, M., Ishibashi, T., Liu, S., Kireeva, M. L., Lubkowska, L., Kashlev, M., & Bustamante, C. J. (2013). Complete dissection of transcription elongation reveals slow translocation of RNA polymerase II in a linear ratchet mechanism. eLife, 2. doi:10.7554/elife.00971Lieberman, K. R., Dahl, J. M., Mai, A. H., Cox, A., Akeson, M., & Wang, H. (2013). Kinetic Mechanism of Translocation and dNTP Binding in Individual DNA Polymerase Complexes. Journal of the American Chemical Society, 135(24), 9149-9155. doi:10.1021/ja403640bLieberman, K. R., Dahl, J. M., Mai, A. H., Akeson, M., & Wang, H. (2012). Dynamics of the Translocation Step Measured in Individual DNA Polymerase Complexes. Journal of the American Chemical Society, 134(45), 18816-18823. doi:10.1021/ja3090302Dahl, J. M., Mai, A. H., Cherf, G. M., Jetha, N. N., Garalde, D. R., Marziali, A., … Lieberman, K. R. (2012). Direct Observation of Translocation in Individual DNA Polymerase Complexes. Journal of Biological Chemistry, 287(16), 13407-13421. doi:10.1074/jbc.m111.338418Rodriguez, I., Lazaro, J. M., Blanco, L., Kamtekar, S., Berman, A. J., Wang, J., … de Vega, M. (2005). A specific subdomain in  29 DNA polymerase confers both processivity and strand-displacement capacity. Proceedings of the National Academy of Sciences, 102(18), 6407-6412. doi:10.1073/pnas.0500597102Morin, J. A., Cao, F. J., Valpuesta, J. M., Carrascosa, J. L., Salas, M., & Ibarra, B. (2012). Manipulation of single polymerase-DNA complexes: A mechanical view of DNA unwinding during replication. Cell Cycle, 11(16), 2967-2968. doi:10.4161/cc.21389Morin, J. A., Cao, F. J., Lazaro, J. M., Arias-Gonzalez, J. R., Valpuesta, J. M., Carrascosa, J. L., … Ibarra, B. (2012). Active DNA unwinding dynamics during processive DNA replication. Proceedings of the National Academy of Sciences, 109(21), 8115-8120. doi:10.1073/pnas.1204759109Ibarra, B., Chemla, Y. R., Plyasunov, S., Smith, S. B., Lázaro, J. M., Salas, M., & Bustamante, C. (2009). Proofreading dynamics of a processive DNA polymerase. The EMBO Journal, 28(18), 2794-2802. doi:10.1038/emboj.2009.219Bustamante, C., Chemla, Y. R., Forde, N. R., & Izhaky, D. (2004). Mechanical Processes in Biochemistry. Annual Review of Biochemistry, 73(1), 705-748. doi:10.1146/annurev.biochem.72.121801.161542Jahnel, M., Behrndt, M., Jannasch, A., Schäffer, E., & Grill, S. W. (2011). Measuring the complete force field of an optical trap. Optics Letters, 36(7), 1260. doi:10.1364/ol.36.001260Soengas, M. S., Esteban, J. A., Lázaro, J. M., Bernad, A., Blasco, M. A., Salas, M., & Blanco, L. (1992). Site-directed mutagenesis at the Exo III motif of phi 29 DNA polymerase; overlapping structural domains for the 3′-5′ exonuclease and strand-displacement activities. The EMBO Journal, 11(11), 4227-4237. doi:10.1002/j.1460-2075.1992.tb05517.xSoengas, M. S., Gutiérrez, C., & Salas, M. (1995). Helix-destabilizing Activity of φ29 Single-stranded DNA Binding Protein: Effect on the Elongation Rate During Strand Displacement DNA Replication. Journal of Molecular Biology, 253(4), 517-529. doi:10.1006/jmbi.1995.0570De Vega, M., Lazaro, J. M., Salas, M., & Blanco, L. (1996). Primer-terminus stabilization at the 3′-5′ exonuclease active site of phi29 DNA polymerase. Involvement of two amino acid residues highly conserved in proofreading DNA polymerases. The EMBO Journal, 15(5), 1182-1192. doi:10.1002/j.1460-2075.1996.tb00457.xVisscher, K., Schnitzer, M. J., & Block, S. M. (1999). Single kinesin molecules studied with a molecular force clamp. Nature, 400(6740), 184-189. doi:10.1038/22146Pandey, M., & Patel, S. S. (2014). Helicase and Polymerase Move Together Close to the Fork Junction and Copy DNA in One-Nucleotide Steps. Cell Reports, 6(6), 1129-1138. doi:10.1016/j.celrep.2014.02.025Truniger, V. (2002). A positively charged residue of phi29 DNA polymerase, highly conserved in DNA polymerases from families A and B, is involved in binding the incoming nucleotide. Nucleic Acids Research, 30(7), 1483-1492. doi:10.1093/nar/30.7.1483Berman, A. J., Kamtekar, S., Goodman, J. L., Lázaro, J. M., de Vega, M., Blanco, L., … Steitz, T. A. (2007). Structures of phi29 DNA polymerase complexed with substrate: the mechanism of translocation in B-family polymerases. The EMBO Journal, 26(14), 3494-3505. doi:10.1038/sj.emboj.7601780Thomen, P., Lopez, P. J., Bockelmann, U., Guillerez, J., Dreyfus, M., & Heslot, F. (2008). T7 RNA Polymerase Studied by Force Measurements Varying Cofactor Concentration. Biophysical Journal, 95(5), 2423-2433. doi:10.1529/biophysj.107.125096Keller, D., & Bustamante, C. (2000). The Mechanochemistry of Molecular Motors. Biophysical Journal, 78(2), 541-556. doi:10.1016/s0006-3495(00)76615-xHerbert, K. M., Greenleaf, W. J., & Block, S. M. (2008). Single-Molecule Studies of RNA Polymerase: Motoring Along. Annual Review of Biochemistry, 77(1), 149-176. doi:10.1146/annurev.biochem.77.073106.100741Wong, I., Patel, S. S., & Johnson, K. A. (1991). An induced-fit kinetic mechanism for DNA replication fidelity: direct measurement by single-turnover kinetics. Biochemistry, 30(2), 526-537. doi:10.1021/bi00216a030Lowe, L. G., & Guengerich, F. P. (1996). Steady-State and Pre-Steady-State Kinetic Analysis of dNTP Insertion Opposite 8-Oxo-7,8-dihydroguanine byEscherichia coliPolymerases I exo-and II exo- †. Biochemistry, 35(30), 9840-9849. doi:10.1021/bi960485xKirmizialtin, S., Nguyen, V., Johnson, K. A., & Elber, R. (2012). How Conformational Dynamics of DNA Polymerase Select Correct Substrates: Experiments and Simulations. Structure, 20(4), 618-627. doi:10.1016/j.str.2012.02.018Donlin, M. J., Patel, S. S., & Johnson, K. A. (1991). Kinetic partitioning between the exonuclease and polymerase sites in DNA error correction. Biochemistry, 30(2), 538-546. doi:10.1021/bi00216a031Li, Y. (1998). Crystal structures of open and closed forms of binary and ternary complexes of the large fragment of Thermus aquaticus DNA polymerase I: structural basis for nucleotide incorporation. The EMBO Journal, 17(24), 7514-7525. doi:10.1093/emboj/17.24.7514Lieberman, K. R., Dahl, J. M., & Wang, H. (2014). Kinetic Mechanism at the Branchpoint between the DNA Synthesis and Editing Pathways in Individual DNA Polymerase Complexes. Journal of the American Chemical Society, 136(19), 7117-7131. doi:10.1021/ja5026408Subuddhi, U., Hogg, M., & Reha-Krantz, L. J. (2008). Use of 2-Aminopurine Fluorescence To Study the Role of the β Hairpin in the Proofreading Pathway Catalyzed by the Phage T4 and RB69 DNA Polymerases†. Biochemistry, 47(23), 6130-6137. doi:10.1021/bi800211fShamoo, Y., & Steitz, T. A. (1999). Building a Replisome from Interacting Pieces. Cell, 99(2), 155-166. doi:10.1016/s0092-8674(00)81647-5Lamichhane, R., Berezhna, S. Y., Gill, J. P., Van der Schans, E., & Millar, D. P. (2013). Dynamics of Site Switching in DNA Polymerase. Journal of the American Chemical Society, 135(12), 4735-4742. doi:10.1021/ja311641bKamtekar, S., Berman, A. J., Wang, J., Lázaro, J. M., de Vega, M., Blanco, L., … Steitz, T. A. (2004). Insights into Strand Displacement and Processivity from the Crystal Structure of the Protein-Primed DNA Polymerase of Bacteriophage φ29. Molecular Cell, 16(4), 609-618. doi:10.1016/j.molcel.2004.10.019Hogg, M., Wallace, S. S., & Doublié, S. (2004). Crystallographic snapshots of a replicative DNA polymerase encountering an abasic site. The EMBO Journal, 23(7), 1483-1493. doi:10.1038/sj.emboj.7600150Seifert, U. (2012). Stochastic thermodynamics, fluctuation theorems and molecular machines. Reports on Progress in Physics, 75(12), 126001. doi:10.1088/0034-4885/75/12/126001Cao, F. J., & Feito, M. (2009). Thermodynamics of feedback controlled systems. Physical Review E, 79(4). doi:10.1103/physreve.79.041118Cao, F. J., Dinis, L., & Parrondo, J. M. R. (2004). Feedback Control in a Collective Flashing Ratchet. Physical Review Letters, 93(4). doi:10.1103/physrevlett.93.040603Bier, M. (2007). The stepping motor protein as a feedback control ratchet. Biosystems, 88(3), 301-307. doi:10.1016/j.biosystems.2006.07.013Astumian, R. D. (1997). Thermodynamics and Kinetics of a Brownian Motor. Science, 276(5314), 917-922. doi:10.1126/science.276.5314.917Komissarova, N., & Kashlev, M. (1997). Transcriptional arrest: Escherichia coli RNA polymerase translocates backward, leaving the 3’ end of the RNA intact and extruded. Proceedings of the National Academy of Sciences, 94(5), 1755-1760. doi:10.1073/pnas.94.5.1755Brueckner, F., & Cramer, P. (2008). Structural basis of transcription inhibition by α-amanitin and implications for RNA polymerase II translocation. Nature Structural & Molecular Biology, 15(8), 811-818. doi:10.1038/nsmb.145

Open Problems on Information and Feedback Controlled Systems

Feedback or closed-loop control allows dynamical systems to increase their performance up to a limit imposed by the second law of thermodynamics. It is expected that within this limit, the system performance increases as the controller uses more information about the system. However, despite the relevant progresses made recently, a general and complete formal development to justify this statement using information theory is still lacking. We present here the state-of-the-art and the main open problems that include aspects of the redundancy of correlated operations of feedback control and the continuous operation of feedback control. Complete answers to these questions are required to firmly establish the thermodynamics of feedback controlled systems. Other relevant open questions concern the implications of the theoretical results for the limitations in the performance of feedback controlled flashing ratchets, and for the operation and performance of nanotechnology devices and biological systems.Comment: LaTeX, 10 pages, 2 figures. Improved version to appear in Entrop