Self-assembly of biological macromolecules.

The genetic apparatus of the cell is responsible for the accurate biosynthesis of the primary structure of macromolecules which then spontaneously fold up and, in certain circumstances, aggregate to yield the complex tertiary and quaternary structures of the biologically active molecules. Structures capable of self-assembly in this range from simple monomers through oligomers to complex multimeric structures that may contain more than one type of polypeptide chain and components other than protein. It is becoming clear that even with the simpler monomeric enzymes there is becoming clear that even with the simpler monomeric enzymes there is a kinetically determined pathway for the folding process and that a folded protein must now be regarded as the minimum free energy form of the kinetically accessible conformations. It is argued that the denatured subunits of oligomeric enzymes are likely to fold to something like their final structure before aggregating to give the native quaternary structure and the available evidence would suggest that this is so. The importance of nucleation events and stable intermediates in the self-assembly of more complex structures is clear. Many self-assembling structures contain only identical subunits and symmetry arguments are very successful in accounting for the structures formed. Because proteins are themselves complex molecules and not inelastic geometric objects, the rules of strict symmetry can be bent and quasi-equivalent bonding between subunits permitted. This possibility is frequently employed in biological structures. Conversely, symmetry arguments can offer a reliable means of choosing between alternative models for a given structure. It can be seen that proteins gain stability by growing larger and it is argued in evolutionary terms that aggregation of subunits is the preferred way to increase the size of proteins. The possession of quaternary structure by enzymes allows conferral of other biologically important properties, such as cooperativity between active sites, changes of specificity, substrate channelling and sequential reactions within a multi-enzyme complex. Comparison is made of the invariant subunit compositions of the simpler oligomeric enzymes with the variation evidently open to, say, the 2-oxoacid dehydrogenase complexes of E. coli. With viruses, on the other hand, the function of the quaternary structure is to package nucleic acid and, as an example, the assembly and breakdown of tobacco mosaic virus is discussed. Attention is drawn to the possible ways in which the principles of self-assembly can be extended to make structures more complicated than those that can be formed by simple aggregation of the comonent parts.     

Modeling of biological tree structures

Biological tree-like structures, such as mammalian tracheobronchial airways, are complicated branching systems. One problem in modeling such systems is the reassignment of the number of segments at a given generation in the model being constructed. A hypothesis is proposed which has successfully been used in modeling mammalian lung airways. Research supported by the National Institute of Environmental Health Sciences through U.S. Department of Energy Contract Number EY-76-C-04-1013.     

Self-assembly of reactive amphiphilic block copolymers as mimetics for biological membranes

Over the years, polymers have attracted a great deal of interest because they offer a unique platform for the development of materials in fields as diverse as biomedicine and packaging. Many of these purposes use polymers that had been developed for totally different applications. Recently, however, chemical tailoring and molecular and supramolecular control of the chemistry and, thus, the physical and biological response have become a key interest of many researchers. In particular, systems that operate in aqueous media have become an intensely researched field. This is mostly because many devices must be biocompatible, which implies that they have to function in aqueous solutions. Over the past few years, new approaches for mimicking cell surfaces, for generating biocompatible and bioactive drug delivery systems, and for directed targeting have been developed. One recent development is polymeric systems with an enhanced biofunctionality, such as amphiphilic block copolymers that can act as mimetics for biological membranes. Because there are virtually no limits to combinations of monomers, biological and synthetic building blocks, ligands, receptors, and other proteins, polymer hybrid materials show a great promise for applications in biomedicine and biotechnology.     

Self-assembly of biopolymeric structures below the threshold of random cross-link percolation.

Self-assembly of extended structures via cross-linking of individual biomolecules often occurs in solutions at concentrations well below the estimated threshold for random cross-link percolation. This requires solute-solute correlations. Here we study bovine serum albumin. Its unfolding causes the appearance of an instability region of the sol, not observed for native bovine serum albumin. As a consequence, spinodal demixing of the sol is observed. The thermodynamic phase transition corresponding to this demixing is the determinative symmetry-breaking step allowing the subsequent occurrence of (correlated) cross-linking and its progress up to the topological phase transition of gelation. The occurrence of this sequence is of marked interest to theories of spontaneous symmetry-breaking leading to morphogenesis, as well as to percolation theories. The present results extend the validity of conclusions drawn from our previous studies of other systems, by showing in one single case, system features that we have hitherto observed separately in different systems. Time-resolved experimental observations of the present type also bring kinetic and diffusional processes and solute-solvent interactions into the picture of cross-link percolation.     

Self-assembly of extracellular tubular structures of non-protein nature produced by an actinomycete]

When grown on the solid synthetic medium with glucose as the only carbon source the dedifferentiated "fructose" mutant of Actinomyces roseoflavus var. roseofungini accumulated aggregates of tubular-like structures. The individual tubules had the internal diametre of 80 A and external diametre of approximately 200-220 A. These structures were isolated as a distinct fraction and their non-protein nature was demonstrated. They were easily soluble in acetone and reconstitutable in vitro. The possible significance of production of self-assembling structures by a mutant with impaired differentiation is discussed. The possibility of involvement of self-assembly processes in the formation of surface sheath of aerial mycelium in normally differentiating actinomycetes is mentioned.     

Magnetic stimulation for non-homogeneous biological structures

Background  

Magnetic stimulation has gained relatively wide application in studying nervous system structures. This technology has the advantage of reduced excitation of sensory nerve endings, and hence results in quasi-painless action. It has become clinically accepted modality for brain stimulation. However, theoretical and practical solutions for assessment of induced current distribution need more detailed and accurate consideration.     

Unconventional modes for STEM imaging of biological structures

In this paper recent developments are discussed in instrumentation and methodology associated with scanning transmission electron microscopes (STEM), which are of great potential interest for solving structural and chemical problems in biological specimens. After describing the main features of the instrument, an attempt is made to define which type of signal acquisition and processing is best suited to obtain a given type of information. Starting with a definition of cross sections of interest, a discussion follows of methods using angular selection, energy selection of the transmitted beam, and several ways of signal mixing. More specific attention is devoted to two main modes of processing signals: ratio contrast, which emphasizes slight changes in scattering factors, rather independent of thickness variations; and elemental mapping, which provides semi-quantitative information on the distribution of low Z elements of great significance in biological specimens. Data relevant to typical biological objects are presented and discussed; they allow for the definition of the capabilities and limitations of these methods. These unconventional imaging modes define a new attitude for improving the efficiency of this modern generation of electron microscopes.     

Lipid exchange and transfer between biological lipid-protein structures

The dynamic state of membrane and lipoprotein lipids is all the more impressive when the complexity of lipoprotein and membrane structure is considered. For as long as such a ubiquitous and easily demonstrable process has been studied, the mechanism(s) of lipid exchange is still unknown. Is a direct contact between lipoproteins and membranes required for lipid exchange, or are molecules expelled from lipid-protein complexes to spend a transient existence in the aqueous environment before returning to their donor or being accomodated in another complex? Although recent studies suggest the certain proteins such as the phospholipid exchange proteins can exert some vectoral and selective control over exchange reactions, the exchange of lipids, as studied under most conditionsin vitro, seems to be a random occurrence and a purely physicochemical event. Ifin vitro studies are indeed reflective of the processesin vivo, the lipid exchange activity in a cell can likely be depicted as shown in Figure 18.     

Theory of intermolecular electron transfer in nanoscale biological structures

Macromolecular biological systems performing directed electron transfer are nano-sized structures. The distance between carrier molecules (cofactors), which represent practically isolated electron localization centers, reaches tens of angstroms. The electron transfer theory based on the concept of delocalized electron states, which is conventionally used in biophysics, is unable to adequately interpret the results of concrete observations in many cases. On the basis of the theory of electronic transitions in the case of localized states, developed in the physics of disordered matter, a mechanism of long-distance electron transfer in biological systems is suggested. The molecular relaxation of the microenvironment of electron localization centers that accompanies the electron transfer process is also considered.     

Theory of long-distance electron transfer in nanoscale biological structures

Macromolecular biological systems accomplishing the directed electron transfer are nano-sized structures. The distance between carrier molecules (cofactors), which represent practically isolated electron localization centers, reaches tens of angstroms. The electron transfer theory based on the concept of delocalized electron states, which is conventionally used in biophysics, is unable to adequately interpret the results of concrete observations in many cases. On the basis of the theory of electronic transitions in the case of localized states, developed in the physics of disorder matter, a mechanism of long distance electron transfer in biological systems is suggested. The molecular relaxation of the microenvironment of electron localization centers that accompanies the electron transfer process is also considered.     

Prions of fungi: inherited structures and biological roles

The term 'prion' means an infectious protein that does not need an accompanying nucleic acid. There are six fungal prions, including four self-propagating amyloids and two enzymes that are necessary to activate their inactive precursors. Here we explore the scope of the prion phenomenon, the biological and evolutionary roles of prions, the structural basis of the amyloid prions and the prominent role of chaperones (proteins that affect the folding of other proteins) and other cellular components in prion generation and propagation.     

Quantitative evaluation of the allometric transformation of of biological structures

Detection and quantification of allometry is a crucial problem in understanding morphological changes, both for systematic and morphogenetic purposes. A section of S.A.M. (Shape Analytical Morphometry) software system was used for this attempt. It consists of the following steps: a) boundary detection; b) starting point detection; c) size normalization; d) extraction of the fundamental shape by Kth order polynomials; e) finding of symmetry evaluator (S.A.E.) by means of a second degree equation. This last procedure gives an arc-chord complex that expresses a vector for allometry where intercept value was for application point, first degree coefficient was for direction and second degree coefficient was for modulus and versus. The main parameters, isometry fraction and allometry fraction may be understood referring them to morphogenetic models.     

Information content of chemical structures and some possible biological applications

The purpose of this paper is to calculate the amount of information contained in a chemical or biological structure, and to estimate the energy needed for obtaining an organization unit. The first problem is solved by applying H. J. Morowitz's reasoning (Bull. Math. Biophysics,17, 81–86, 1955) and, for the second one, calculations based upon bond formation heat are carried out.Information content theoretical physical entropy, real physical entropy, informational entropy or negentropy entropic information or neginformation, heat amount, as well as relationships between these system parameters, are defined and used. The investigation covers 63 chemical substances (inorganic and organic compounds). The numerical results should show that common organized systems happen to be between two extreme kinds of systems: highly disordered systems and ideally organized systems. Some speculative numerical applications are carried out regarding chlorophyllian photosynthesis and information amount accumulated through biological growth. It seems that Information Theory may predict some biocalorimetric results.