Mathematics of Ions in Channels and Solutions: Stochastic Derivations, Direct, Variational and Inverse Solutions that fit Data

By Bob Eisenberg

Rush University Medical Center, Chicago, IL

Published on

Abstract

Ion channels have a role in biology like the channels of field effect transistors in computers: both are valves for electricity controlling nearly everything. Ion channels are proteins with a hole down their middle that catalyze the movement of sodium, potassium, calcium and chloride ions across the otherwise impermeable membranes that define cells. Once a channel opens, it has a single structure on the biological time scale slower than say 2 microseconds. The ions present around every cell and molecule in biology are hard spheres and so the calculation of how hard spheres go through a channel of one structure is a central problem in a wide range of biology. Literally thousands of biologists study the properties of channels in experiments every day. My collaborators and I have shown how the relevant equations can be derived (almost) from stochastic differential equations, and how they can be solved in inverse, variational, and direct problems using models that describe a wide range of biological situations with only a handful of parameters that do not change even when concentrations change by a factor of 10^7. Variational methods hold particular promise as a way to solve problems outstanding for more than a century because they describe interactions of 'everything with everything' else that characterise ions crowded into channels.

Bio

Bob Eisenberg is interested in studying ion channels as physical objects, trying to use the tools of physics, chemistry, engineering, and applied mathematics to understand how they work. Ion channels are proteins with a hole down their middle that are the gatekeepers for cells. Ion channels control an enormous range of biological function in health and disease. But ion channels have simple enough structure that they can be analyzed with the usual tools of physical science. With that analysis in hand, Bob and John Tang, with gifted collaborators, are trying to design practical machines that use ion channels.

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Department of Mathematics Computational and Applied Mathematics Seminar

Cite this work

Researchers should cite this work as follows:

  • Bob Eisenberg (2014), "Mathematics of Ions in Channels and Solutions: Stochastic Derivations, Direct, Variational and Inverse Solutions that fit Data," https://nanohub.org/resources/20271.

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Time

Location

REC 316, Purdue University, West Lafayette, IN

Tags

Mathematics of Molecular Biology
  • Mathematics of Molecular Biology 1. Mathematics of Molecular Biolo… 0
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  • A few atoms make a BIG Difference 2. A few atoms make a BIG Differe… 199.83316649983317
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  • General Theme Mathematics of Molecular Biology 3. General Theme Mathematics of M… 375.67567567567568
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  • How does it work? 4. How does it work? 481.51484818151488
    00:00/00:00
  • Ion Channels are the Valves of Cells Ion 5. Ion Channels are the Valves of… 488.98898898898904
    00:00/00:00
  • Ion Channels are Biological Devices 6. Ion Channels are Biological De… 714.18084751418087
    00:00/00:00
  • Channels are Selective Molecular Devices 7. Channels are Selective Molecul… 1273.8071404738073
    00:00/00:00
  • Different Types of Channels use Different Types of Ions 8. Different Types of Channels us… 1275.342008675342
    00:00/00:00
  • Multi-Scale Issues are Always Present 9. Multi-Scale Issues are Always … 1298.4651317984651
    00:00/00:00
  • Thousands of Molecular Biologists Study Channels as Devices 10. Thousands of Molecular Biologi… 1312.2455789122457
    00:00/00:00
  • SINGLE isolated RyR Channels 11. SINGLE isolated RyR Channels 1421.5882549215883
    00:00/00:00
  • Channel Structure Does Not Change 12. Channel Structure Does Not Cha… 1429.0290290290291
    00:00/00:00
  • Where to start? 13. Where to start? 1515.2485819152487
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  • Atomic Scale Engineering 14. Atomic Scale Engineering 1521.0543877210544
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  • Uncalibrated Simulations will make devices that do not work 15. Uncalibrated Simulations will … 1604.8715382048715
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  • Where to start? 16. Where to start? 1647.8812145478812
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  • Reduced Models are Needed 17. Reduced Models are Needed 1675.6423089756424
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  • Biology is Easier than Physics 18. Biology is Easier than Physics 1691.4247580914248
    00:00/00:00
  • Multi-scale Engineering is MUCH easier when robust 19. Multi-scale Engineering is MUC… 1746.8802135468802
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  • Reduced models exist 20. Reduced models exist 1750.0166833500168
    00:00/00:00
  • Inverse Problems 21. Inverse Problems 1754.9883216549883
    00:00/00:00
  • Bioengineers: this is reverse engineering 22. Bioengineers: this is reverse … 1796.3630296963631
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  • Ill posed problems 23. Ill posed problems 1851.5515515515517
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  • Inverse Problems: many answers possible 24. Inverse Problems: many answers… 1853.31998665332
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  • Molecular Dynamics usually yields ONE data point 25. Molecular Dynamics usually yie… 1917.017017017017
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  • Crowded Ions and Side Chains 26. Crowded Ions and Side Chains 1918.3516850183517
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  • Ions are Crowded 27. Ions are Crowded 1949.84984984985
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  • Crowded Active Sites in 573 Enzymes 28. Crowded Active Sites in 573 En… 2045.6456456456458
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  • EC2: TRANSFERASES 29. EC2: TRANSFERASES 2133.4668001334667
    00:00/00:00
  • Everything Interacts with Everything Else 30. Everything Interacts with Ever… 2150.1501501501502
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  • Stochastic PDE and Field Theory 31. Stochastic PDE and Field Theor… 2199.9332665999332
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  • Always start with Trajectories 32. Always start with Trajectories 2387.3206539873208
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  • From Trajectories to Probabilities 33. From Trajectories to Probabili… 2539.3393393393394
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  • Trajectories in Condensed Phases are Noisy 34. Trajectories in Condensed Phas… 2567.867867867868
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  • Theory of Stochastic Processes 35. Theory of Stochastic Processes 2627.3606940273608
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  • Langevin Equations Bulk Solution 36. Langevin Equations Bulk Soluti… 2638.9723056389726
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  • Electric Force 37. Electric Force 2797.4307640974307
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  • Sum the traqjectories 38. Sum the traqjectories 2810.2102102102103
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  • More Math Many papers 39. More Math Many papers 2815.4821488154821
    00:00/00:00
  • Device Equation 40. Device Equation 2877.5775775775778
    00:00/00:00
  • Conditional PNP 41. Conditional PNP 2897.3973973973975
    00:00/00:00
  • Probability and Conditional Probability 42. Probability and Conditional Pr… 3047.4474474474478
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  • Conditioning and Correlations 43. Conditioning and Correlations 3067.0337003670338
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  • Kirchoff's Current Law 44. Kirchoff's Current Law 3077.8778778778778
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  • Science, not Mathematics 45. Science, not Mathematics 3185.3186519853189
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  • Everything Interacts 46. Everything Interacts 3189.5895895895897
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  • Poisson-Nernst-Planck 47. Poisson-Nernst-Planck 3191.9586252919589
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  • Semiconductor Equations 48. Semiconductor Equations 3215.2152152152153
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  • Counting at low resolution gives 'Semiconductor Equations' 49. Counting at low resolution giv… 3237.4374374374374
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  • Solution of PNP Equation 50. Solution of PNP Equation 3248.0146813480146
    00:00/00:00
  • Solution was actually DERIVED 51. Solution was actually DERIVED 3275.8425091758427
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  • Solution of PNP Equation 52. Solution of PNP Equation 3299.5995995995995
    00:00/00:00
  • Solution of Langevin Equation 53. Solution of Langevin Equation 3303.16983650317
    00:00/00:00
  • Solution of Langevin Equation 54. Solution of Langevin Equation 3306.63997330664
    00:00/00:00
  • Overwhelming effoect of Correlations 55. Overwhelming effoect of Correl… 3343.677010343677
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  • Classical Chemistry ignores Correlations 56. Classical Chemistry ignores Co… 3348.8822155488824
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  • Theory of Ideal Gases 57. Theory of Ideal Gases 3437.4040707374043
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  • Generalization of 'Law' of Mass Action 58. Generalization of 'Law' of Mas… 3439.2392392392394
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  • The Law of Mass Action 59. The Law of Mass Action 3539.3393393393394
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  • Law of Mass Action 60. Law of Mass Action 3543.1097764431097
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  • Nothing is Ideal! 61. Nothing is Ideal! 3544.4444444444448
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  • Highly Compressible Plasma 62. Highly Compressible Plasma 3547.8812145478814
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  • Ionic Solutions are Complex Fluids 63. Ionic Solutions are Complex Fl… 3623.0563897230563
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  • Everything is hidden 64. Everything is hidden 3652.2856189522859
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  • Law of Mass Action 65. Law of Mass Action 3655.0884217550883
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  • Macroscopic Models are True INDEPENDENT 66. Macroscopic Models are True IN… 3735.5355355355355
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  • Inconsistent with Conservation of Charge 67. Inconsistent with Conservation… 3740.2736069402736
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  • All BIOLOGY OCCURS IN CHARGED SYSTEMS 68. All BIOLOGY OCCURS IN CHARGED … 3741.3079746413082
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  • Inconsistent Treatments 69. Inconsistent Treatments 3742.7093760427097
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