Standard measurements, elasticity values and tensile strength behavior of the human mandible, a contribution to the biomechanics of the mandible--I

This paper is intended to help to characterize the physiological behavior of compact bone structure, so that realistic account can be taken of it when performing finite element (FE) analysis with the aim of solving biomechanical problems. In addition, further knowledge about the complex mechanical behavior of bone structure is provided. In accordance with anthropometric considerations, 13 mandibles have been measured, and a standard mandible defined for use in representative model calculations. In 4 mandibles (fully dentulous, partly dentulous, edentulous), orthotropic mechanical behavior of the fresh bone was determined experimentally. A comparison was also made with published data, as well as our own unpublished data obtained in other bone structures. Orthotropic behavior of the bone structure was confirmed. The material data of the individual bone structure vary considerably, but remain within a certain range. The proportion of the direction-dependent data is, however, almost constant. Our data correspond well with published data, although a direct comparison with the data of the mandible was not possible. A comparison of the data with those from the lower and upper extremities shows significant differences in rigidity, Young's modulus, and extension. A gradation can be found--starting with a maximum--that reveals the following order: mandible, upper extremity, lower extremity. In the case of extension, this order is reversed.     

Mechanical energy expenditure on human movement and the anthropomorphic mechanism]

Mechanical energy expenditures of the man and anthropomorphic locomotion machine during movement are compared theoretically. Sources of the mechanical energy affecting movement of human's lower extremity are modelled by 8 muscles, 3 of which are the two-joint muscles. The model of the lower extremity of anthropomorphic locomotion machine is moved by joint moments. It was shown that in the same movement the model of the human lower extremity can spend less mechanical energy than that of the model of the anthropomorphic locomotion machine. It is caused by the presence of two-joint muscles in the first model. Such an economy of mechanical energy expenditures realized by the two-joint muscle is possible at simultaneous execution of three conditions: 1) signs of the muscle powers, which are produced by that muscle at both joints, are opposite; 2) moments produced by that muscle at each of both joints have the same direction with the joint moments at these joints; 3) one-joint antagonistic muscles are not active. An expression which makes it possible to estimate the mechanical energy savings by the two-joint muscles during humans' movement was developed.     

Synthesis and characterization of novel blood-compatible soluble chemically cross-linked polyurethanes with excellent mechanical performance for biomedical applications

A controlled cross-linking polymerization system was designed, and soluble chemically cross-linked polyurethane was synthesized using laurylamine, n-octylamine, n-pentylamine, and ethylenediamine chain extenders. The mechanical analysis showed that the polyurethane materials synthesized in this paper have very excellent mechanical properties with a breaking elongation of 1914% and a tensile strength of 4303 N/cm(2). Such good mechanical properties must enable it to have good longevity when used as biomaterials. The polyurethane materials with n-pentylamine and n-octylamine chain extenders show reduced platelet adhesion than that with an ethylenediamine chain extender after sustaining 200 000 times of load cycles, indicating that polyurethanes introduced with an alkyl side chain onto the hard segments keep good antithrombogenic properties after sustaining load cycles. This might be because the hard segments are shielded by the alkyl side chain when the micro-phase-separation structure is destroyed in the repeated deformation of the polyurethane materials. The present investigation reveals that the influence of introducing long alkyl side chains into the backbone of the polyurethane macromolecule has been shown to reduce platelet deposition and to enhance in vitro albumin adsorption. However, in this paper, it has been observed that the polyurethane material introduced with a proper-length alkyl side chain onto the hard segment has the best antithrombogenic properties after the fatigue test.     

Body shape and differences between species

The variation of body shape among prosimians is reviewed. Special emphasis is placed on the selective advantages, that is the mechanical reasons, to which variants of the locomotor apparatus can be traced back. There are differences found in the cheiridia, but at present they cannot be explained in terms of mechanics; there is nearly no knowledge about the mechanical meaning of their diversity. Myological characteristics of taxa can be explained mechanically, but this has not yet been done. Well known are variations of body proportions. These discriminate higher taxa, and are largely coincident with the often-used locomotor categories. In spite of this, there are only few sound arguments about the real biomechanic value of characteristic proportions for a given locomotor mode. What is known on this field, is reviewed. Progress can be made only, if the mechanical conditions, set by postural behavior and locomotion, are understood completely. The subtle distinctions between lower taxonomic units can normally be identified only on the basis of detailed and quantified analyses of movements on one hand, and of biometrics on the other. In the few cases in which such studies have been made, the differences of morphology fit to the mechanical requirements of locomotion which also differ only in quantitative details.     

An upper body model for the kinematical analysis of the joint chain of the human arm

The diagnosis and treatment of many orthopaedic and neurological disorders can benefit from movement analysis of the upper extremities by facilitating an objective and quantitative assessment of the compensatory movement strategies of patients. In this paper, a procedure for upper extremity movement analysis is introduced, which allows the simultaneous measurement of movement in all anatomical axes of the kinematical joint chain of the upper body. In first clinical applications it was shown that the procedure facilitates the detection of pathological movement patterns and therefore, adds significantly to the understanding of upper extremity movement strategies.     

Design of superior spider silk: from nanostructure to mechanical properties

Spider dragline silk is of practical interest because of its excellent mechanical properties. However, the structure of this material is still largely unknown. In this article, we report what we believe is a new model of the hierarchical structure of silk based on scanning electron microscope and atomic force microscope images. This hierarchical structure includes beta-sheet, polypeptide chain network, and silk fibril. It turns out that an exceptionally high strength of the spider dragline silk can be obtained by decreasing the size of the crystalline nodes in the polypeptide chain network while increasing the degree of orientation of the crystalline nodes. Based on this understanding, how the reeling speed affects mechanical properties of spider dragline silk can be understood properly. Hopefully, the understanding obtained in this study will shed light on the formation of spider silk, and consequently, on the principles for the design of ultrastrong silk.     

Studies on the Structure of Feather Keratin: II. A β-Helix Model for the Structure of Feather Keratin

The assumption that the proline residues in feather keratin, which comprise 12 per cent of the total, are periodically located along the polypeptide chain is shown to lead to an essentially unique structure for this fibrous protein. The structure is based on a β-helix; i.e., an extended chain which coils slowly to form a helix of relatively large pitch. Such helices tend to aggregate by hydrogen bonding to form cylindrical units, which in turn can aggregate further into cable-like structures. This model has been tested with respect to its predictions concerning the x-ray diffraction pattern, infrared spectrum, mechanical properties, and chemical behavior of feather keratin. Preliminary results indicate that it is better capable of accounting for the data than previously proposed structures.     

The influence of altering push force effectiveness on upper extremity demand during wheelchair propulsion

Manual wheelchair propulsion has been linked to a high incidence of overuse injury and pain in the upper extremity, which may be caused by the high load requirements and low mechanical efficiency of the task. Previous studies have suggested that poor mechanical efficiency may be due to a low effective handrim force (i.e. applied force that is not directed tangential to the handrim). As a result, studies attempting to reduce upper extremity demand have used various measures of force effectiveness (e.g., fraction effective force, FEF) as a guide for modifying propulsion technique, developing rehabilitation programs and configuring wheelchairs. However, the relationship between FEF and upper extremity demand is not well understood. The purpose of this study was to use forward dynamics simulations of wheelchair propulsion to determine the influence of FEF on upper extremity demand by quantifying individual muscle stress, work and handrim force contributions at different values of FEF. Simulations maximizing and minimizing FEF resulted in higher average muscle stresses (23% and 112%) and total muscle work (28% and 71%) compared to a nominal FEF simulation. The maximal FEF simulation also shifted muscle use from muscles crossing the elbow to those at the shoulder (e.g., rotator cuff muscles), placing greater demand on shoulder muscles during propulsion. The optimal FEF value appears to represent a balance between increasing push force effectiveness to increase mechanical efficiency and minimize upper extremity demand. Thus, care should be taken in using force effectiveness as a metric to reduce upper extremity demand.     

States and transitions during forced unfolding of a single spectrin repeat

Spectrin is a vital and abundant protein of the cytoskeleton. It has an elongated structure that is made by a chain of so-called spectrin repeats. Each repeat contains three antiparallel alpha-helices that form a coiled-coil structure. Spectrin forms an oligomeric structure that is able to cross-link actin filaments. In red cells, the spectrin/actin meshwork underlying cell membrane is thought to be responsible for special elastic properties of the cell. In order to determine mechanical unfolding properties of the spectrin repeat, we have used single molecule force spectroscopy to study the states of unfolding of an engineered polymeric protein consisting of identical spectrin domains. We demonstrate that the unfolding of spectrin domains can occur in a stepwise fashion during stretching. The force-extension patterns exhibit features that are compatible with the existence of at least one intermediate between the folded and the completely unfolded conformation. Only those polypeptides that still contain multiple intact repeats display intermediates, indicating a stabilisation effect. Precise force spectroscopy measurements on single molecules using engineered protein constructs reveal states and transitions during the mechanical unfolding of spectrin. Single molecule force spectroscopy appears to open a new window for the analysis of transition probabilities between different conformational states.     

Physics in muscle research

Muscle is one of few organs whose performance can be measured by physical quantities. However, very few attempts have been made to apply theoretical physics to muscle. In this paper we will see how physical principles can be applied by taking advantage of unique properties of muscle structure. The first topic is to establish the stability conditions of sarcomere structure. The conclusions are then compared to some experimental facts. Next, we move on to the field theory fundamentals. The concept of energy density as a stress tensor is shown to be a powerful tool for the dielectric force theory to understand how proteins move under electric fields. By combining the structural stability theory and the dielectric force theory we arrive at a helical dipole array. We discuss the source of strong dipole fields and how the dipole strength could be controlled by Ca ions. The behavior of water and ions under electric fields is briefly discussed. The third topic is the mechanical stiffness of muscle in longitudinal and lateral directions. Some experimental data are shown and the physics of anisotropic stiffness is discussed. An appendix is provided to explain the pitfalls of experimenting with isolated components rather than organized structures (sarcomere).     

The cyclic contryphan motif CPxXPXC, a robust scaffold potentially useful as an omega-conotoxin mimic

Contryphan-R, from venom of the cone-shell Conus radiatus, represents a novel cyclic peptide scaffold onto which residues may be grafted to mimic unrelated protein surfaces. Three substitutions were made at the x and X positions of the disulfide-bridged motif CPxXPXC, where X and x represent any L- and D-handed residues, respectively, P represents proline or hydroxyproline, and C a half-cystine. These substitutions were designed to mimic part of the pharmacophore of the unrelated globular polypeptide omega-conotoxin GVIA, which blocks N-type calcium channels. The structure of this engineered contryphan, YNK-contryphan-R ([D-Tyr4, Asn5, Lys7]contryphan-R), is shown to be similar to that of native contryphan-R (Pallaghy et al., Biochemistry, 1999, Vol. 38, pp. 13553-13559), confirming that the scaffold is robust with respect to the multiple substitutions. In particular, the alpha-beta bond vectors characterising the orientation of the side chains relative to the backbone are similar in contryphan-R, YNK-contryphan-R, and omega-conotoxin GVIA, which is the required result for a scaffold-based approach to molecular design. The solution structure of YNK-contryphan-R has an N-terminal, nonhydrogen-bonded, chain reversal centered on Hyp3-D-Trp4, and a C-terminal type I beta-turn. A minor form due to cis-trans isomerism of the Hyp2-Cys3 peptide bond is present in YNK-contryphan-R in a larger proportion than in contryphan-R. It is evident, particularly from the (3)J(HalphaHN) coupling constants, that YNK-contryphan-R is more flexible than contryphan-R, probably due to the absence in YNK-contryphan-R of the Pro-Trp packing present in the native molecule. Nevertheless, the structure confirms that cyclic peptide molecular designs can achieve the intended conformations.     

A physical model of acoustic effects of ultrahigh frequency fields on biological systems

A physical model of radiosound based on the stimulation of mechanical oscillations in liquid media at adsorption of SHF impulse energy is presented. It is shown that a limited liquid volume can be considered as an acoustic resonator with self oscillation frequency. At definite relationships between the succession frequency and impulse duration interference takes place. Oscillograms of recorded mechanical oscillations are presented. The low frequency type of radiosound is explained. A conclusion is made concerning the reliability of the proposed method for investigating radiosound.     

Joit torque and energy patterns in normal gait

Experiments were conducted on normal level gait to determine the synergistic patterns present in the forces causing joint moments and those associated with the generation, absorption and transfer of mechanical energy. The following generalizations can be made about the patterns: (i) During swing phase three forces (gravitational, muscle and knee joint acceleration) are responsible for shank rotation, and are shown to act together during both acceleration and deceleration.—(ii) The patterns of generation, absorption and transfer of mechanical energy at the joints are detailed. These patterns demonstrate inter-segment transfers of energy through the joint centres, and through the muscles, as well as the more recognized generation and absorption by the muscles themselves.—As a result of the complexity shown in these patterns it is cautioned that fundamental relationships that may have been derived from controlled biomechanical experiments (such as horizontal flexion and extension of the forearm) are not likely to apply to more normal movements such as gait.     

On the use of deuterium nuclear magnetic resonance as a probe of chain packing in lipid bilayers

The packing of hydrocarbon chains in the bilayers of lamellar (L alpha) phases of soap/water and phospholipid/water mixtures has been studied by deuterium NMR spectroscopy and X-ray diffraction. A universal correlation is shown to exist between the average C-D bond order parameter SCD of hydrocarbon chains and the average area per chain ach, irrespective of the chemical structure of the surfactant (hydrophilic group, number of chains per molecule, and chain length), composition, and temperature. The practical utility of the correlation is illustrated by its application to the characterization of the distribution of various hydrophobic and amphiphilic solutes in bilayers. The distribution of hydrocarbons within a bilayer is shown to depend upon their molecular structure in a manner which highlights the nature of the molecular interactions involved. For example, benzene is shown to be fairly uniformly distributed across the bilayer with an increasing tendency to distribute into the center at high concentrations. In contrast, the more complex hydrocarbon tetradecane preferentially distributes into the center of the bilayer at low concentrations, while at higher concentrations it intercalates between the surfactant chains. Alcohols such as benzyl alcohol, octanol, and decanol all interact similarly with the bilayer in so far as they are pinned to the polar/apolar interface, presumably by involvement of the hydroxyl group in a hydrogen bond. But the response of the surfactant chains to the void volume created in the center of the bilayer is dependent upon the distance of penetration of the alcohol into the bilayer. For benzyl alcohol, the shortest molecule, this void volume is taken up by the disordering of the chains, while for decanol, the longest molecule, it is absorbed by interdigitation of the chains of apposing monolayers. For octanol, the chain interdigitation mechanism is dominant at low concentrations, but there is a transition to chain disordering at high concentrations. Finally, it is shown that the correlation provides a useful test for statistical mechanical models of chain ordering in lipid bilayers.     

On the optimal folding of protein molecules

The process of formation of a globular structure by a long molecular chain has been examined. In this process, various regions of the chain interact with one another. We classify the contacts thus formed as “correct” and “erroneous” ones. The correct contacts are those characteristic of the final native globular structure. All other contacts can be treated as erroneous. It is demonstrated that globule formation may proceed actually without formation and subsequent decay of erroneous contacts. Our model permits avoiding examination of numerous erroneous variants inasmuch as the regions of the chain that form correct contacts enter “long-range” interactions that at the same time can be highly selective. The existence of interactions of this kind facilitates the mutual approach and interaction of just those regions of the chain that yield correct contacts. Based on database analysis, it is shown that the model is valid not only for abstract structures but also for real polypeptide chains capable of forming protein globules and helical fibrils.     

Transition state in the folding of alpha-lactalbumin probed by the 6-120 disulfide bond.

The guanidine hydrochloride concentration dependence of the folding and unfolding rate constants of a derivative of alpha-lactalbumin, in which the 6-120 disulfide bond is selectively reduced and S-carboxymethylated, was measured and compared with that of disulfide-intact alpha-lactalbumin. The concentration dependence of the folding and unfolding rate constants was analyzed on the basis of the two alternative models, the intermediate-controlled folding model and the multiple-pathway folding model, that we had proposed previously. All of the data supported the multiple-pathway folding model. Therefore, the molten globule state that accumulates at an early stage of folding of alpha-lactalbumin is not an obligatory intermediate. The cleavage of the 6-120 disulfide bond resulted in acceleration of unfolding without changing the refolding rate, indicating that the loop closed by the 6-120 disulfide bond is unfolded in the transition state. It is theoretically shown that the chain entropy gain on removing the cross-link from a random coil chain with helical stretches can be comparable to that from an entirely random chain. Therefore, the present result is not inconsistent with the known structure in the molten globule intermediate. Based on this result and other knowledge obtained so far, the structure in the transition state of the folding reaction of alpha-lactalbumin is discussed.     

Packing and recognition of protein structural elements: A new approach applied to the 4-helix bundle of myohemerythrin

We present a novel search strategy for determining the optimal packing of protein secondary structure elements. The approach is based on conformational energy optimization using a predetermined set of side chain rotamers and appropriate methods for sampling the conformational space of peptide fragments having fixed backbone geometries. An application to the 4-helix bundle of myohemerythrin is presented. It is shown that the conformations of the amino acid side chains are largely determined at the level of helix pairs and that superposition of these results can be used to construct the full bundle. The final solution obtained, taking into account restrictions due to the lateral amphiphilicity of the helices, differs from the native structure by only a 20° rotation of a single helix. © 1993 Wiley-Liss, Inc.     

Isoalloxazine derivatives promote photocleavage of natural RNAs at G.U base pairs embedded within helices.

We have recently shown that isoalloxazine derivatives are able to photocleave RNA specifically at G.U base pairs embedded within a helical stack. The reaction involves the selective molecular recognition of G.U base pairs by the isoalloxazine ring and the removal of one nucleoside downstream of the uracil residue. Divalent metal ions are absolutely required for cleavage. Here we extend our studies to complex natural RNA molecules with known secondary and tertiary structures, such as tRNAs and a group I intron (td). G.U pairs were cleaved in accordance with the phylogenetically and experimentally derived secondary and tertiary structures. Tandem G.U pairs or certain G.U pairs located at a helix extremity were not affected. These new cleavage data, together with the RNA crystal structure, allowed us to perform molecular dynamics simulations to provide a structural basis for the observed specificity. We present a stable structural model for the ternary complex of the G. U-containing helical stack, the isoalloxazine molecule and a metal ion. This model provides significant new insight into several aspects of the cleavage phenomenon, mechanism and specificity for G. U pairs. Our study shows that in large natural RNAs a secondary structure motif made of an unusual base pair can be recognized and cleaved with high specificity by a low molecular weight molecule. This photocleavage reaction thus opens up the possibility of probing the accessibility of G.U base pairs, which are endowed with specific structural and functional roles in numerous structured and catalytic RNAs and interactions of RNA with proteins, in folded RNAs.