Thursday, September 25, 2008

Functional Physics of Life

Functional Physics of
Biomolecular Self-organization

Wolfgang Hebel *
Abstract
Although it has been possible to discover the complicated structures of many bio-molecules in recent decades, especially of the famous DNA and of many proteins with an amazing precision down to the level of their atomic detail, nevertheless, a fundamental understanding of the functional molecular physics in a living cell eludes us. All molecular processes that occur inside a living organism serve one principal purpose, namely to sustain life by replacing the actual molecular system at the appropriate moment with an essentially identical, but younger one. However, our classical physics knows of no basic principle that distinguishes such purposeful molecular processes in living organisms from ordinary molecular reactions in inanimate matter. This study discusses a fundamental premise that underlies apparently the functioning of biomolecular self-organization.

Introduction
The astounding property of a living cell resides in its ability to build up autonomously its own molecular structures and to self-organise its functioning according to a basic plan programmed into the molecular structure of its DNA. The functioning of a living cell takes place in close contact with its molecular environment, as the cell imports and exports molecules following the fundamental instructions communicated by its DNA complex. Scientifically, the innumerable molecular reactions of such cellular self-organization prove bewilderingly complex and are still barely understood, because our traditional principles of classical physics are not completely adequate to make us understand how the well-coordinated teamwork of thousands of millions of individual molecules in a living cell can purposefully function. Classical physics does not include, for example, any Principle of Information & Communication between the partners of a system to make them function for a given aim. However, of all molecular reactions theoretically possible in the complex environment of a living cell, priority goes to those that serve the purpose coded into the DNA complex. This basic knowledge on the functioning of life has to be communicated and acknowledged by all molecular players in a living cell in order to meet the programmed goal. What are the physical foundations of this self-organized molecular interplay in a living cell? Can some advanced physics make us understand the amazing functionality of living matter? [4]
For more than twenty years, the author has been participating at plenty of high-level scientific meetings related to bio-molecular topics [1] including the traditional Nobel Laureate meetings at Lindau, Germany, end of June every year [3]. At those meetings, he regularly encountered such fundamental questions as aforementioned, inspiring him to write down his view on the functional physics of biomolecular self-organization.


* EU Scientific Coordinator retd., Brussels, 1st September 2008
Email: wolfgang.hebel@telenet.be



Molecular Recognition
The greatest challenge confronting molecular biology today is to lift bit by bit the veil of mystery around the biophysical chemistry that governs the functioning of living cells [1]. In recent years, a term was coined to describe as best as we can the concept of the observed phenomena: Molecular Self-assembly, while admitting that we know very little about the underlying rules. Fundamental bio-molecular research has only just begun to explain the physics of molecular self-organization [2]. Why does this astounding property of living cells exist at all? In other words, what is the origin of life? This will no doubt remain an open question for some time to come.
Advances in experimental methods and techniques, which are today increasingly available to fundamental bio-molecular research, are fortunately bringing a constant progress in our scientific knowledge. One notable example of this is the discovery by Dagmar RINGE (Waltham, MA, USA), which she presented at the Workshop on molecular Biotechnology held in Jena, Germany, in November 1994. Under the title The role of the solvent in molecular recognition, she explained her experimental findings, which worked from a principle often neglected in model studies, namely that the ubiquitous water molecules present in a cell are not only there to act as a solvent, but also they compete as binding partner. A layer of water molecules covers all molecular structures in the cytoplasm including the proteins, the main functional players of the cell. This protects them from binding with unauthorized reaction partners, of which there are many in the cell, quite capable in principle of binding to any protein if the chance occurred. The omnipresent covering layer of water molecules, however, prevents this. The protective water only moves aside to permit binding when the right partner for the functional process presents itself. This typically occurs when the favored partner molecule can correctly dock with the atomic structure of a given protein. Mutual molecular recognition ensures that only those molecules can bind which belong together from the functional point of view.
Dagmar RINGE’s discovery is therefore of fundamental significance making it easier to understand how molecular self-assembly in living cells can come about. She obtained her study results using highly developed NMR spectroscopy, which enabled her to ‘see’ virtually individual water molecules. She demonstrated experimentally that a protein and its authorized partner molecule fit together in atomic detail like a safety key in its lock. The protective layer of water molecules on the surface of the functional partner only allow passage when the ‘chemistry between the partners is right’, to use a common expression, in other words, when the nanoscopic attraction vectors between the protein and its authorized partner molecule are stronger than toward the ubiquitous water molecules. When this happens, the water molecules are forced away and the protein exposes its binding site.
Despite innumerable advances on the level of detail such as the findings mentioned above, we still have little or no understanding of the functional orchestration of myriads of individual molecules in a living cell. The highly complex interactions, which they undergo to achieve the predetermined purpose, continue to puzzle science in the absence of an overarching functional mechanism that would clarify our understanding.


Cellular Communication
The aforementioned experimental findings together with related knowledge gained over years by attending scientific conferences, led me to examine more intensely the mysterious functioning mechanisms in living organisms and to propose the following hypothesis by way of explanation.
When a protein binds with a preferred partner molecule, it changes its geometrical form by folding and adopting a specific conformation. Usually, it is enabled to do so by means of a protein kinase, a small molecular compound, which provides the protein the necessary energy. The cell’s universal energy provider is the well-known, phosphorus-containing compound called ATP (Adenosine TriPhosphate) and the process therefore is called (reversible) protein phosphorylation. This process - discovered by Edmond FISCHER, Nobel Prize 1992 [3] - plays a crucial role in all functional molecular reactions that take place in a cell. When the protein adopts its specific conformation, it is not only its own shape that changes, but its submicroscopic environment in the cytoplasm as well. Many other electrically charged (ionic) particles are present there, including electrons, hydrogen ions (protons), and a large number of different ionized molecules. All these are mobile to various degrees in the aqueous cytoplasm, and the change in the shape of the protein has the effect of slightly altering their position at that moment. The associated electrons change track, they are redirected into different pathways since the cytoplasm is an electrically conducting medium. Unlike an ordinary electrolyte, however, it is in addition intelligently structured.
Normally, all ionized molecular structures are located in well-defined, three-dimensional networks of nanoscopic vectors, which maintain them in their actual position or, if changes occur, displace them in a specific way. It is mainly the easily mobile electrons, which are involved in such cases, moving along other pathways, on electron highways as it were, to new well-defined destinations in the cytoplasm. Their arrival signals that something in the ionic network of the cytoplasm has changed and sets in train a cascade of resulting electronic reactions. However, the electronic signal from a single protein that changes conformation is too weak to have any consequence amid the electronic background noise of the cytoplasm. It is when a whole number of protein molecules folds simultaneously that it becomes a concerted action producing a functional effect. Many electrons in the region around these proteins are mobilized and a grand landslide of electronic pathways takes place, so signaling that a given protein population has bound its partner molecules. The conformational change of the proteins therefore is announced with electronic rapidity, in the shortest possible time at all interlinked locations in the cytoplasm and the scheduled follow-on reactions are set in motion. This requires of course a communication and information centre in the cell, to which all significant events are reported: it is the all-knowing DNA complex in the nucleus of the cell. The arriving electronic signals cause the relevant genes to be switched on or off via complicated molecular pathways, so that the active protein population of the cytoplasm can be adjusted as quickly as possible to suit the signaled changes in accordance with the programmed plan of the cell.
One important aspect of this speculative functional dynamics in the cytoplasm is that every change in the nanoscopic network of ionic bonds between the molecular partners is passed on instantly. This is actually the case as the signal is transmitted electronically. In this way, genetically programmed follow-on reactions can be brought about quasi simultaneously at various locations in the cell, so that they are all linked in a logic manner. The simultaneously launched electronic feedback signals serve not only to report-back that a pre-programmed protein action has been performed, but at the same time, they act as feed-ahead-signals to initiate new, predetermined processes. In this way, the myriad molecular reactions in the complex functional system of the cell are efficiently linked, as both kinds of signal, the feedback and feed-ahead signal arrive practically at the same moment at their respective receptors. Many thousands of simultaneous molecular processes in the cell can so be coordinated effectively to concerted actions, because the electronic signal transmission in a carefully structured ionic network allows the huge amount of information coded in the DNA to be activated instantly in order to master any, whatsoever complex situation. In other words, the active protein population of the cytoplasm can be instructed immediately to suit the signals that have been received by the DNA complex as well from inside the cell as from its molecular environment.
Of course, the constant production and transport of appropriate proteins as well as the dismantling of faulty or surplus proteins (protein waste) take relatively much longer time (microseconds) than the original electronic signals (femtoseconds), as those tasks involve considerable atomic masses being thousands of times heavier than the tiny, elementary electrons. Electronic signaling, therefore, has to precede and accompany all molecular reactions in the cellular plasma in view of making such bewilderingly complex molecular system operate efficiently according to the instructions stored in the DNA complex.

Conclusion
As mentioned at the outset, the functional mechanism outlined here is speculative and for the lack of detail experimental evidence, it is described only in broad terms. Finally, the situation will be found more complicated than this, but my intention was simply to set out an idea on the functional physics of bio-molecular self-organization and to initiate scientific discussion. Nevertheless, the concept of electronic signal transmission via predetermined routes in living cells is more than a mere imagination. It can call, for example, upon experimental findings of recent detail studies on photoelectrons released in light harvesting proteins of bacteria and plant cells (chlorophyll) by incident sunlight [1]. These photoelectrons bring about the well-known photosynthesis or biosynthesis of molecules vital to life on Earth.


References:
[1] Wolfgang Hebel: The Mystery of Life, Does science hold the key?
German University Press, Baden-Baden, 2007
[2] Christof Biebricher, Gregoire Nicolis, Peter Schuster:
Self-organisation in the physico-chemical and Life Sciences
European Commission, Luxembourg, 1995, Report EUR 16546
[3] Wolfgang Hebel: Nobel Laureates meet Students, Lindau 1996-2005,
On the edge of knowledge, German University Press, Baden-Baden, 2008
[4] Ilya Prigogine: The End of Certainty – Time, Chaos, and the new Laws of Nature
The Free Press, New York, 1997
[5] Manfred Eigen: Stufen zum Leben
R. Piper, München, 1987