A Theory of Mesoscopic Phenomena: Time Scales, Emergent Unpredictability, Symmetry Breaking and Dynamics Across Different Levels

Integrating symmetry breaking originally advanced by Anderson, bifurcation from nonlinear dynamical systems, Landau's phenomenological theory of phase transition, and the mechanism of emergent rare events first studied by Kramers, we propose a mathematical representation for mesoscopic dynamics which links fast motions below (microscopic), movements within each discrete state (intra-basin-of-attraction) at the middle, and slow inter-attractor transitions with rates exponentially dependent upon the size of the system. The theory represents the fast dynamics by a stochastic process and the mid-level by a nonlinear dynamics. Multiple attractors arise as emergent properties. The interplay between the stochastic element and nonlinearity, the essence of Kramers' theory, leads to successive jump-like transitions among different basins. We describe each transition as a dynamic symmetry breaking exhibiting Thom-Zeeman catastrophe and phase transition with the breakdown of ergodicity (differentiation). The dynamics of a nonlinear mesoscopic system is not deterministic, rather it is a discrete stochastic jump process. Both the Markov transitions and the very discrete states are emergent phenomena. This emergent inter-attractor stochastic dynamics then serves as the stochastic element for the nonlinear dynamics of a level higher (aggregates) on an even larger spatial and longer time scales (evolution). The mathematical theory captures the hierarchical structure outlined by Anderson and articulates two types of limit of a mesoscopic dynamics: A long-time ensemble thermodynamics in terms of time t, followed by the size of the system N, tending infinity, and a short-time trajectory steady state with N tending infinity followed by t tending infinity. With these limits, symmetry breaking and cusp catastrophe are two perspectives of a same mesoscopic system on different time scales.

[1]  Wei-mou Zheng A Simple Model for the First-Order Phase Transition and Met astability , 1993 .

[2]  Hong Qian,et al.  Thermodynamic limit of a nonequilibrium steady state: Maxwell-type construction for a bistable biochemical system. , 2009, Physical review letters.

[3]  R. Marcus,et al.  Electron transfers in chemistry and biology , 1985 .

[4]  H. Haken Synergetics: an Introduction, Nonequilibrium Phase Transitions and Self-organization in Physics, Chemistry, and Biology , 1977 .

[5]  H. Kramers Brownian motion in a field of force and the diffusion model of chemical reactions , 1940 .

[6]  Jacques Monod,et al.  A Biologist's World View. (Book Reviews: Chance and Necessity. An Essay on the Natural Philosophy of Modern Biology) , 1972 .

[7]  René Lefever,et al.  Comment on the kinetic potential and the maxwell construction in non-equilibrium chemical phase transitions , 1977 .

[8]  Peter G. Wolynes,et al.  Biomolecules: Where the Physics of Complexity and Simplicity Meet , 1994 .

[9]  R. Penrose,et al.  A theory of everything? , 2005, Nature.

[10]  F. Zhang,et al.  The potential and flux landscape theory of evolution. , 2012, The Journal of chemical physics.

[11]  L. Hood,et al.  Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution. , 2008, Medical hypotheses.

[12]  J. Hopfield Physics, Computation, and Why Biology Looks so Different , 1994 .

[13]  James D. Murray Mathematical Biology: I. An Introduction , 2007 .

[14]  Wolynes,et al.  Intermittency of single molecule reaction dynamics in fluctuating environments. , 1995, Physical review letters.

[15]  P. Ao Emerging of Stochastic Dynamical Equalities and Steady State Thermodynamics from Darwinian Dynamics. , 2008, Communications in theoretical physics.

[16]  M. Esposito,et al.  Dissipative quantum dynamics in terms of a reduced density matrix distributed over the environment energy , 2004 .

[17]  Jin Wang,et al.  Quantifying the underlying landscape and paths of cancer , 2014, Journal of The Royal Society Interface.

[18]  H. Qian Cooperativity in cellular biochemical processes: noise-enhanced sensitivity, fluctuating enzyme, bistability with nonlinear feedback, and other mechanisms for sigmoidal responses. , 2012, Annual review of biophysics.

[19]  Hermann Haken,et al.  Information and Self-Organization: A Macroscopic Approach to Complex Systems , 2010 .

[20]  H. Qian Nonlinear stochastic dynamics of mesoscopic homogeneous biochemical reaction systems—an analytical theory , 2011 .

[21]  T. D. Lee,et al.  Statistical Theory of Equations of State and Phase Transitions. I. Theory of Condensation , 1952 .

[22]  Zhedong Zhang,et al.  Curl flux, coherence, and population landscape of molecular systems: nonequilibrium quantum steady state, energy (charge) transport, and thermodynamics. , 2014, The Journal of chemical physics.

[23]  Urs P. Wild,et al.  Single-molecule spectroscopy. , 1997, Annual review of physical chemistry.

[24]  J. Onuchic,et al.  Navigating the folding routes , 1995, Science.

[25]  Jin Wang,et al.  Funneled Landscape Leads to Robustness of Cell Networks: Yeast Cell Cycle , 2006, PLoS Comput. Biol..

[26]  Jin Wang,et al.  Kinetic paths, time scale, and underlying landscapes: a path integral framework to study global natures of nonequilibrium systems and networks. , 2010, The Journal of chemical physics.

[27]  Han Shao,et al.  Symmetry and physics , 2000 .

[28]  U. Seifert Stochastic thermodynamics, fluctuation theorems and molecular machines , 2012, Reports on progress in physics. Physical Society.

[29]  A. Leggett,et al.  Dynamics of the dissipative two-state system , 1987 .

[30]  Kenneth Dixon,et al.  Introduction to Stochastic Modeling , 2011 .

[31]  Hong Qian,et al.  Chemical Biophysics: Quantitative Analysis of Cellular Systems , 2008 .

[32]  H. Qian,et al.  Mesoscopic biochemical basis of isogenetic inheritance and canalization: stochasticity, nonlinearity, and emergent landscape. , 2012, Molecular & cellular biomechanics : MCB.

[33]  H. Eyring The Activated Complex in Chemical Reactions , 1935 .

[34]  Hong Qian,et al.  Non-equilibrium phase transition in mesoscopic biochemical systems: from stochastic to nonlinear dynamics and beyond , 2011, Journal of The Royal Society Interface.

[35]  J. Onuchic,et al.  Self-regulating gene: an exact solution. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[36]  P. Wolynes,et al.  The middle way. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Jerker Widengren,et al.  Single Molecule Spectroscopy in Chemistry, Physics and Biology , 2010 .

[38]  Sui Huang,et al.  The potential landscape of genetic circuits imposes the arrow of time in stem cell differentiation. , 2010, Biophysical journal.

[39]  Yuhai Tu,et al.  Effects of adaptation in maintaining high sensitivity over a wide range of backgrounds for Escherichia coli chemotaxis. , 2007, Biophysical journal.

[40]  Erkang Wang,et al.  Potential and flux landscapes quantify the stability and robustness of budding yeast cell cycle network , 2010, Proceedings of the National Academy of Sciences.

[41]  R. Graham Macroscopic potentials, bifurcations and noise in dissipative systems , 1987 .

[42]  H. Feng,et al.  Non-equilibrium transition state rate theory , 2014 .

[43]  Hong Qian,et al.  Stochastic dynamics and non-equilibrium thermodynamics of a bistable chemical system: the Schlögl model revisited , 2009, Journal of The Royal Society Interface.

[44]  Peter G Wolynes,et al.  Stochastic gene expression as a many-body problem , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Jin Wang,et al.  Potential landscape and flux framework of nonequilibrium networks: Robustness, dissipation, and coherence of biochemical oscillations , 2008, Proceedings of the National Academy of Sciences.

[46]  Jin Wang,et al.  Quantifying robustness and dissipation cost of yeast cell cycle network: the funneled energy landscape perspectives. , 2007, Biophysical journal.

[47]  S. Kauffman,et al.  Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective. , 2009, Seminars in cell & developmental biology.

[48]  René Thom,et al.  Structural stability and morphogenesis , 1977, Pattern Recognit..

[49]  P. Wolynes,et al.  The energy landscapes and motions of proteins. , 1991, Science.

[50]  Haidong Feng,et al.  Potential and flux decomposition for dynamical systems and non-equilibrium thermodynamics: curvature, gauge field, and generalized fluctuation-dissipation theorem. , 2011, The Journal of chemical physics.

[51]  Miroslav Grmela,et al.  Role of thermodynamics in multiscale physics , 2013, Comput. Math. Appl..

[52]  P. Hänggi,et al.  Reaction-rate theory: fifty years after Kramers , 1990 .

[53]  Jin Wang,et al.  Potential Energy Landscape and Robustness of a Gene Regulatory Network: Toggle Switch , 2007, PLoS Comput. Biol..

[54]  D. Lathrop Nonlinear Dynamics and Chaos: With Applications to Physics, Biology, Chemistry, and Engineering , 2015 .

[55]  H. Frauenfelder,et al.  Proteins are paradigms of stochastic complexity , 2005 .

[56]  H. Qian Cellular Biology in Terms of Stochastic Nonlinear Biochemical Dynamics: Emergent Properties, Isogenetic Variations and Chemical System Inheritability , 2010 .

[57]  Dick Bedeaux,et al.  Mesoscopic non-equilibrium thermodynamics for quantum systems , 2001 .

[58]  Yuhai Tu,et al.  The energy-speed-accuracy tradeoff in sensory adaptation , 2012, Nature Physics.

[59]  K. Dill,et al.  Markov processes follow from the principle of maximum caliber. , 2011, The Journal of chemical physics.

[60]  H. Qian,et al.  Analytical Mechanics in Stochastic Dynamics: Most Probable Path, Large-Deviation Rate Function and Hamilton-Jacobi Equation , 2012, 1205.6052.

[61]  Landscape and global stability of nonadiabatic and adiabatic oscillations in a gene network. , 2012, Biophysical journal.

[62]  Joseph A. Bank,et al.  Supporting Online Material Materials and Methods Figs. S1 to S10 Table S1 References Movies S1 to S3 Atomic-level Characterization of the Structural Dynamics of Proteins , 2022 .

[63]  Gaite,et al.  Phase transitions as catastrophes: The tricritical point. , 1990, Physical review. A, Atomic, molecular, and optical physics.

[64]  R. Thom Structural stability and morphogenesis , 1977, Pattern Recognition.

[65]  Jin Wang,et al.  Quantifying the Waddington landscape and biological paths for development and differentiation , 2011, Proceedings of the National Academy of Sciences.

[66]  Hong Qian,et al.  Stochastic theory of nonequilibrium steady states and its applications. Part I , 2012 .

[67]  Lewis Campbell,et al.  The Life of James Clerk Maxwell , .

[68]  Jin Wang,et al.  Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction , 2008, Proceedings of the National Academy of Sciences.

[69]  P. Wolynes,et al.  Symmetry and the energy landscapes of biomolecules. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[70]  Philip W. Anderson,et al.  More Is Different Broken symmetry and the nature of the hierarchical structure of science , 1972 .

[71]  H. Qian,et al.  A quantitative analysis of single protein-ligand complex separation with the atomic force microscope. , 1997, Biophysical chemistry.