Protocols & related links

P1: Preface to the proceedings of the ICTP conference “Nonlinear cooperative phenomena in biological systems” held at Trieste, Miramare, 19-22 August 1977.

Research in nonlinear, cooperative phenomena in biological systems has mainly been concentrated on a few subjects such as neural networks and different subcellular phenomena, e.g. protein folding and solitary waves, each of which have become fields of their own, but to less extent on dynamics at the level of a single cell for which many vital functions are at work in the start and during the cell cycle. Needless to say, the living cell consists of condensed matter, and without correlations on membranes, protein and DNA-backboones, the cell could not function such as in differentiation and division. No signals would be transduced and there would be no life. Much of this normal “wild type” behaviour of a cell, living today, could often be better understood through studies of mutants and transformed cell lines, and through knowledge of the principles for selection and evolution.

Cellular dynamics and molecular assembly into biological systems are problems with a vast interface to physics. However, several important differences with respect to inanimate matter must be underlined. A biological system is usually more complex with large variations in order parameters and coefficients that control the interpolation between harmonic and displacive interaction modes. Moreover, this is not due to temperature variations. In contrast to inanimate matter systems, mostly driven thermally, living systems are chemically open and usually regulated lyotropically by various reactant concentrations, at chemically non-stationary conditions and at rather constant temperatures.

Thus many biological substances can form liquid crystalline structures in an aqueous environment, for instance cell membranes, provided that the concentration of the substrate reaches a saturation point at given temperature. Although temperature is still an important variable in determining the phase present, the concentration of one component with respect to the others is far more important. Hence, the behaviour of such a system is more lyotropic than thermotropic. This is even more pronounced for the various humoral factors reacting at the surface membrane, such as antigens, hormones and their receptors, the interaction of which regulates and drives the entire cell cycle dynamics in a quantal all-or-none fashion.
Studies in cellular metabolism thus take a new direction. From an initial stage of pathway identification, followed by a period of studies of pathway regulation through cooperativity, phosphorylation, feedback, feedforward and allostery, experiments now indicate that we have come to an era of pathway quantification. For instance, one single molecule can make the whole difference between cell division and premature abortion. This is fortunate because, if this was not the case the high fidelity in DNA replication would probably not be guaranteed and we would not exist. Thus the cell coherently counts the number of signals received, a behaviour that also indicates a more robust, solid like structure near the quantal threshold at high concentrations of reactants, after a rather liquid, displacive dynamics at low concentrations that permits the reactants to diffuse about in order to strategically meet. What we call “life” could then eventually be observed as fluctuations on the edge between order and chaos.

This awakes an old dream of a non-equilibrium statistical physics for biology, at the same time as it reveals the problems of stationary and thermotropic type theories when applied to non-equilibrium phenomena, and chemically open, lyotropically regulated systems. For instance, internalization of activated receptors takes place long before a stationary state is developed. This excludes the use of Hill, Langmuir and Michaelis-Menthen equations in this context, and of chemically stationary Ising and lattice type models, which reduce to the ordinary Langmuir response in the limit of vanishing cooperativity. The problems with such models could also be identified through a wrong scaling behaviour and a threshold for response up to three orders of magnitude different from the assessed one.
The perplexing discovery that a dividing cell counts the number of signals received, which indicates an almost perfect coherence, might eventually also provide evidence for organized nonlinear excitations in biological systems. However, much to my regret, there was not sufficient time for a discussion of non-equilibrium statistical physics in chemically open and lyotropic systems. Therefore, also the question of driving mechanism for living systems came a little aside. A short summary of that part, compiled by Dieterich Stauffer, is published in this volume, which also includes a number of abstracts.

The aim of the meeting was to bring together researchers from different fields and to somewhat bridge the gap between experiments and theory. Despite the fact that we did not fully managed, according to the response, the meeting was a success. The scientific committee of this conference entitled “Nonlinear cooperative phenomena in biological systems”, included Giorgio Careri (University of Rome), Stuart Kauffman (Santa Fee Institute), and Leif Matsson (University of Gothenburg and Chalmers). Discussions with Per Bak, Hans Frauenfelder, Stig Lundquist, and Dieterich Stauffer also contributed significantly to the qualities of the meeting.
The order of contents of this book follows that of the speakers. Thereafter follows two reports by contributors who unfortunately could not participate, one on neural networks by Gerard Toulouse and a second one on ligand gated ion channels in chemically open systems. This is followed by a section of abstracts, and a short summary of the panel discussion.

Finally I want to thank the International Centre for Theoretical Physics (ICTP), its director Miguel Virasoro, Yu Lu and Hilda Cerdeira for the opportunity of holding this conference at ICTP. I also thank the administrative staff, in particular Valery Shaw, for their kindness and efficiency in all the arrangements and hope that all participants enjoyed the meeting as I did myself. I also thank Reymond Emanuelsson for typing five of the contributed manuscripts in the correct formate. At an early stage in the planning of the meeting Stig Lundquist suggested that it should be held at ICTP, and performed as an Adriatico Research Conference. As the leader of this series of conferences in condensed matter physics at ICTP, during three decades, parallel to his many activities at the University of Gothenburg and Chalmers, the Royal Swedish Academy of Sciences, the Nobel Committee for Physics and many other things, he has also stimulated this type of interdisciplinary activities. It is therefore a pleasure for me to dedicate this volume to Stig Lundquist.

Leif Matsson
Editor

P2: Preface to the proceedings of the “First Workshop on biological physics 2000” held at Chulalongkorn University, Bangkok, 18-22 September 2000.

A workshop on biological physics was helf in Bankok, Thailand, on 18-22 September 2000. Biological Physics, once a small part of physics in which a few devoted and possibly far-sighted physicists tried to build a new direction, has become a rapidly growing field. The workshop in Bangkok was planned to survey the field.

Biological Physics covers an enormous number of interesting subfields. A living cell, for instance, is a chemically open system in which many essential biological functions are non-equilibrium nonlinear collective phenomena, driven by chemical reactants such as ATP, GTP, different ligands and receptors. The living cell and many of its subsystems such as proteins, membranes, cytoskeleton with microtubules, and the nucleus with the DNA double helix and the centrosome, are hence lyotropic systems depending on various reactant concentrations.

One central problem is what molecules can do collectively in living matter that they cannot do in inanimate matter. In other words, what is the phenomenon of life expressed in terms of the collective behavior of the constituent molecules. Without correlations between biomolecules, for instance receptors engaged by their ligands, there would be no life. Both nonlocal and local correlations are prerequisites for instance for signal transduction and DNA replication. A description of biological phenomena, experimentally studied at a molecular level, thus requires an extensive physical modeling with the full arsenal of tools and knowledge of many-body physics derived from studies of inanimate matter. However, biological systems are far more complex than the systems encountered in ordinary condensed matter physics. A central problem of biological physics thus is to start from what is known and then to study experimentally, theoretically, and computationally the new phenomena encountered in biosystems in order to create novel nonequilibrium models. This approach may lead to an understanding of the nature of biological functions. Thus one of the aims of the conference was to bridge the gap between experiment and theory and to bring together researchers from different fields.

The order of contents of this book follows that in which the talks were given at the meeting. One of the contributions, the one by Wokyung Sung, was published previously and is therefore included here in the form of an extended abstract. The meeting was economically supported by National Research Council of Thailand (NRCT), Thailand Research Fund (TRF), Asia Pacific Center for Theoretical Physics (APCTP), Third World Academy of Sciences (TWAS), and Chulalongkorn University, which are here gratefully acknowledged. We also thank Forum for Theoretical Science (FTS), Chulalongkorn University, for all the arrangements before and during the conference. Many cordial thanks are also directed to Associate Professor Chaiyute Thunpithayakul, Associate Professor Wichit Sritrakool, Mr. Chanin Churrahmun, Mr. Piyapol Anubuddhangkura, and students of the FTS whose help made the Workshop a fruitful event.

On behalf of all visiting participators, two of us, Hans Frauenfelder and Leif Matsson, particularly want to thank the hosts, Virulh Sa-yakanit and all others in the FTS, for all the care extended to us. It created a warm atmosphere, which contributed to the quality of the meeting, and which we carried home with us as an unforgettable memory. Finally we sincerely thank Mr Piyapol Anubuddhangkora for his valuable assistance in preparing and editing the manuscripts for the proceedings.

Virulh Sa-yakanit
Leif Matsson
Hans Frauenfelder
Directors and Editors

P3: Preface to the proceedings of the “5th international conference on biological physics” held at Gothenburg University and Chalmers University of Technology, Gothenburg, 23-27 August 2004.

Without the tools of modern physics the structure of DNA would not have been discovered in 1953. The knowledge of the DNA structure in turn initiated the rapid development in molecular biology that we have seen during the last 50 years. It lead to the present detailed but from modeling aspects still qualitative understanding of phenomena, such as, gene regulation, DNA replication and division of cells, to mention just some. A quantitative understanding, for instance, of the dynamics of native DNA and its replication, however, requires the use of methods developed within condensed matter theory because, obviously, a living cell and its DNA consist of condensed matter although perhaps more complex than inanimate matter. In both living and inanimate condensed matter many identical molecules can do things together that the single molecule cannot. Thus, instead of asking what life actually is we could ask what molecules can do together in living matter that they cannot do together in inanimate matter. This may also give information about the origin of life and if there is a genuine difference between the living and nonliving states that could be ascribed to matter as such.

Perhaps life is just an illusion, a romantic concept that we fill with dreams and all sorts of imaginations, avoiding the core problem, the fact that living condensed matter usually defines chemically open, non-equilibrium, lyotropic systems. The dynamics and biological functions of living systems may therefore depend on reactant concentrations. Unfortunately, our present knowledge in physics is mainly about thermotropic systems, in which the interpolation between harmonic and displacive modes of interaction is driven by temperature variations. We have learned to handle non-equilibrium reactions such as those occurring in pattern formation experiments. However, such structures are not sufficiently robust to simulate biological systems. Single molecule experiments have shown that DNA already without the initiator proteins and histones is itself a rather rigid structure. We must therefore also learn to handle non-equilibrium reactions in dynamical systems restricted by correlations between steadily increasing or decreasing numbers of molecules. Apart from extending our physical knowledge beyond the Boltzmann type statistical mechanics, insights in this problem area could perhaps provide a clue to the definition of life. Knowing the dynamics of native DNA, and how to describe DNA replication in normal cells, we could then also have a chance to better understand proliferation of cancer cells.

This special issue of the Journal of Biological Physics contains papers presented at the 5th International Conference on Biological Physics. In the first paper Adrian Parsegian and I make an attempt to summarize some of all interesting material presented at this conference and give a short background. We also present data showing that it was a successful meeting. Thus, for instance, the large majority of some 500 participants, more than 400 of which were from non-host countries, stayed the whole week out.

The planning of the conference was a collaborative effort of a local organizing committee and I want to thank all colleagues who were active in that part of the process. Advice was also taken from the IUPAP commission on biological physics and an international program committee. The committees are listed here below. However, without the economic generosity extended to us by sponsors this meeting could not have taken place. I therefore would like to thank the Royal Swedish Academy of Sciences for generous support given through its Nobel Insititue for Physics, and its Nobel Institute for Chemistry. I am also grateful for economic support from the Swedish Research Council, Göteborg University, and the International Union of Pure and Applied Physics (IUPAP). Finally I would like to cordially thank all participators for the extensive scientific contribution of high quality and for creating a constructive and warm atmosphere during the conference.

Leif Matsson
Guest Editor and
Secretary General