The molecular conformations of fibrous elastin and other proteins

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$638 Journal of Biomechanics 2006, Vol. 39 (Suppl 1) Poster Presentations length, at a frequency range 0.1-20Hz. Dynamic mechanical viscoelastic characteristics, the storage modulus (Es), dissipated energy (hysteresis ratio) (h) and the (collagen phase) high modulus EH, were determined in relation to the frequency of the mechanical load applied. Collagen (Hydroxyprolyne) content was unchanged, at 19.7(2.45)mg/g wet tissue during GLA fixation. Adi-4S dissacharides (Chondroitine Sulphate + Dermatan Sulphate) content was reduced from 540 (BPN) to 225(BPG) ~tg/g wet tissue. Comparing the mechanical characteristics of BPN to BPG, Es remained unchanged, in the region 4.5-5.5 Mpa while EH increased from 6-10 to 15-25 Mpa, depended on the loading frequency. A reduction of EH was computed at the higher frequency range for both, BPN and BPG. h was also increased at each frequency value, from a range 17-30 to 22-30% of the loading energy, changed exponentially with frequency. It was shown that crosslinking with glutaraldehyde altered the biochemical composition of BPN to that of BPG, decreasing GAG content, with accompanied alterations in the dynamic mechanical performance of BE It is suggested that the GAGs content may be considered during the design and chemical modification of biomaterials based on BP and other soft tissues. 4148 Mo-Tu, no. 16 (P67) Mechanical response of fingertip and nail to compressive force N. Sakai, S. Shimawaki. Biomechanics Laboratory, Utsunomiya University, Japan Introduction: In the fingertip deformation to compressive force, the nail shows an important role but there are few literature on it. In this study, we investigated the deformation of both the fingertip and the nail under the compressing force. Methods: Three CCD cameras were set up surroundings the platform of electronic balance and three strain gauges with two axis were placed on the nail surface. Subjects (10 men) pressed the right index finger with the angle of 30, 45, and 60 degrees to the platform with the compressive force of 0 N through 5 N, and a lateral view picture of the fingertip were captured. Area (S) of the fingertip in the lateral view was measured in each video still picture by the Scionimage 4.02. Strain in the nail was measured along the longitudinal and the transverse axis at 100 Hz using the sensor interface. Results: Fingertip area at lateral view was almost constant under load, except 30 degrees of contact angle in which the fingertip area had tendency to decrease according to the increase in compression load. However, there was no significant difference between the average fingertip area and the contact angle. Strain along the longitudinal axis increased according to the compressive force increased, and the strain in the proximal-radial side was significantly larger than the proximal-ulnar side and than the distal side, which data was at 30 degrees of contact angle. However, strain along the transverse axis in the nail was almost constant with no significant difference. Discussion: The nail produces a reaction force in fingertip against the com- pressive force. However, nail strain along the transverse axis was significantly different between the radial and the ulnar side of proximal part, and this fact suggests that the thumb was rotated at compression and the moment around the thumb axis produced the concentration of strain at the radial side of nail. The moment would produce an irregularity in deformation of the fingertip and this fact would also make an irregularity in shape of the contact area between the fingertip and the object plane. Novel extracellular matrix proteins isolated from the cartilaginous skeleton of lamprey include lamprin from the annular cartilage (mouthparts) and other unidentified but associated proteins isolated from the branchial cartilage (gill structure), piston and pericardial sac. These proteins are known to differ slightly in biochemical composition. We use Raman microspectrometry to characterise, amongst other things, the tertiary structure of 'lamprin' purified from these tissues. For fibres of purified nuchal ligament elastin mechanical strain in the physiolog- ical range is associated with changes in polarisation in several Raman bands, but little change in secondary structure. Differences are detected between secondary structures of fibrous elastin and lamprin and its associated proteins. 5667 Mo-Tu, no. 18 (P67) Modelling the skin-breast tissue interface V. Rajagopal, '~ Kvistedal, J.-H. Chung, M.P. Nash, P.M.F. Nielsen. Bioengineering Institute, University ef Auckland, Auckland, New Zealand A number of models have been presented to describe the mechanical behavior of the skin-breast tissue interface [1]. Although models presented have been compared with clinical breast images, to our knowledge, a systematic validation of the individual modelling features has so far not been conducted. We have developed an experimental framework that allows us to test the validity of assumptions in the model by comparing predictions with experimental re- sults using materials such as silicon gels. We have validated our modelling framework for predicting surface deformations of a homogeneous silicon gel phantom [2]. The model predicted surface deformations with an RMS error of 1.8 mm for displacements in the order of 20 mm (the characteristic size of the phantom was 120 mm). We have also tracked internal markers in phantoms and are testing in a similar manner models of the skin-breast tissue inter- face. This paper presents validation results under gravity loading conditions. Experimentally, a sheet of silastic rubber is bonded to the gel phantom. The composite model tightly couples a surface membrane model to a 3D tissue model by adding the appropriate components of the stiffness matrices from the skin and adjacent tissue elements. Mechanical properties of the gel and membrane were characterized using the neo-Hookean strain energy function, with parameters estimated from independent experiments on each material. The phantom was injected with a radio-opaque liquid visible under X-ray. Motion of these internal markers were combined with surface deformations (determined using laser scanning) and compared with model predictions. The overarching aim of modelling breast biomechanics is to provide a physics- based tool for non-rigid registration of information across the various breast imaging modalities in order to aid in the localization and diagnosis of breast tumours. References [1] N Ruiter et al. Finite element simulation of the breast's deformation during mam- mography to generate a deformation model for registration. Bildverarbeitung fiJr die Medizin, 2003. [2] V Rajagopal et al. Finite Element Modelling of Breast Biomechanics: Finding a Reference State. In: 26th IEEE EMBS Conference, 2004. 5682 Mo-Tu, no. 17 (P67) The molecular conformations of fibrous elastin and other proteins E.M. Green, R.E. Ellis, C.P. Winlove. University of Exeter, School efPhysics, Exeter, UK Elastic proteins are a diverse group of extracellular matrix proteins which are widespread amongst both mammalian and non-mammalian species where they have evolved to perform varied but specific functions. All elastic proteins display the property of long-range elasticity, which is unusual amongst pro- teins whose functions generally arise from the existence of rigid secondary structures and highly ordered supramolecular assemblies. The elastic proteins are unusual in both structure and physical properties which are believed to be central to mechanical functions and also to processes including self-assembly and matrix organisation. However, the molecular and supramolecular bases of elastic protein functions are still imperfectly understood. We are addressing these questions for elastin, the principle protein of mammalian elastic tissue and for its evolutionary precursor lamprin, the principle component of the extracellular matrix in jawless agnaganths. The molecular conformation and solution dynamics of the elastin monomer and related peptides have been extensively investigated but less is known about the material in its fibrous form. In the present work we use Raman microspectrometry (model Rennishaw RM1000 equipped with a 785 nm laser) to compare ,J,- and fibrous elastin. In order to explore the molecular bases of elasticity of the fibrous material we also investigate the sensitivity of the conformation to changes in mechanical strain, temperature and swelling medium composition. 6673 Mo-Tu, no. 19 (P67) Computational model of the convection enhanced delivery of large molecules into the striatum of the adult brain D.K. Stiles. Medtronic Neurological, Minneapolis, USA The presence of the blood-brain barrier (BBB) frequently prevents the distri- bution of efficacious drugs to the central nervous system. To overcome this barrier, the drug can be delivered directly into the parenchyma of the brain, allowing for specific targeting of the drug to a region of interest. This approach, called convection enhanced delivery (CED), uses the distribution of velocity due to the injection from the catheter tip to spread the drug further than would be realized with simple diffusion. A computational model has been developed to help determine the specific CED distribution of an intraparenchymal delivery of a large molecule (in this case, 10,000Mr dextran) to the striatum. Using the MRI images of an adult female, a three-dimensional finite-element model (FEM) containing the caudate, putamen, internal capsule, the lateral ventricles and a spherical infusion point has been constructed. All of these structures were surrounded by a generalized white matter/grey matter brain model, to account for the diffusion of the drug into the cortex. Using clinically relevant infusion flowrates, Darcy's law and the convection/diffusion equation were solved, taking into account the anisotropy of the diffusion coefficients and hydraulic permeability in white matter, as well as the interstitial fluid clearance. The drug is modeled as chronically delivered, so both transient and steady- state effects were considered. The results of the model show the volume of distribution of the drug in the extracellular space for various catheter flowrates and concentrations.

Transcript of The molecular conformations of fibrous elastin and other proteins

$638 Journal of Biomechanics 2006, Vol. 39 (Suppl 1) Poster Presentations

length, at a frequency range 0.1-20Hz. Dynamic mechanical viscoelastic characteristics, the storage modulus (Es), dissipated energy (hysteresis ratio) (h) and the (collagen phase) high modulus EH, were determined in relation to the frequency of the mechanical load applied. Collagen (Hydroxyprolyne) content was unchanged, at 19.7(2.45)mg/g wet tissue during GLA fixation. Adi-4S dissacharides (Chondroitine Sulphate + Dermatan Sulphate) content was reduced from 540 (BPN) to 225(BPG) ~tg/g wet tissue. Comparing the mechanical characteristics of BPN to BPG, E s remained unchanged, in the region 4.5-5.5 Mpa while EH increased from 6-10 to 15-25 Mpa, depended on the loading frequency. A reduction of EH was computed at the higher frequency range for both, BPN and BPG. h was also increased at each frequency value, from a range 17-30 to 22-30% of the loading energy, changed exponentially with frequency. It was shown that crosslinking with glutaraldehyde altered the biochemical composition of BPN to that of BPG, decreasing GAG content, with accompanied alterations in the dynamic mechanical performance of BE It is suggested that the GAGs content may be considered during the design and chemical modification of biomaterials based on BP and other soft tissues.

4148 Mo-Tu, no. 16 (P67) Mechanical response of fingertip and nail to compressive force N. Sakai, S. Shimawaki. Biomechanics Laboratory, Utsunomiya University, Japan

Introduction: In the fingertip deformation to compressive force, the nail shows an important role but there are few literature on it. In this study, we investigated the deformation of both the fingertip and the nail under the compressing force. Methods: Three CCD cameras were set up surroundings the platform of electronic balance and three strain gauges with two axis were placed on the nail surface. Subjects (10 men) pressed the right index finger with the angle of 30, 45, and 60 degrees to the platform with the compressive force of 0 N through 5 N, and a lateral view picture of the fingertip were captured. Area (S) of the fingertip in the lateral view was measured in each video still picture by the Scionimage 4.02. Strain in the nail was measured along the longitudinal and the transverse axis at 100 Hz using the sensor interface. Results: Fingertip area at lateral view was almost constant under load, except 30 degrees of contact angle in which the fingertip area had tendency to decrease according to the increase in compression load. However, there was no significant difference between the average fingertip area and the contact angle. Strain along the longitudinal axis increased according to the compressive force increased, and the strain in the proximal-radial side was significantly larger than the proximal-ulnar side and than the distal side, which data was at 30 degrees of contact angle. However, strain along the transverse axis in the nail was almost constant with no significant difference. Discussion: The nail produces a reaction force in fingertip against the com- pressive force. However, nail strain along the transverse axis was significantly different between the radial and the ulnar side of proximal part, and this fact suggests that the thumb was rotated at compression and the moment around the thumb axis produced the concentration of strain at the radial side of nail. The moment would produce an irregularity in deformation of the fingertip and this fact would also make an irregularity in shape of the contact area between the fingertip and the object plane.

Novel extracellular matrix proteins isolated from the cartilaginous skeleton of lamprey include lamprin from the annular cartilage (mouthparts) and other unidentified but associated proteins isolated from the branchial cartilage (gill structure), piston and pericardial sac. These proteins are known to differ slightly in biochemical composition. We use Raman microspectrometry to characterise, amongst other things, the tertiary structure of 'lamprin' purified from these tissues. For fibres of purified nuchal ligament elastin mechanical strain in the physiolog- ical range is associated with changes in polarisation in several Raman bands, but little change in secondary structure. Differences are detected between secondary structures of fibrous elastin and lamprin and its associated proteins.

5667 Mo-Tu, no. 18 (P67) Modelling the skin-breast tissue interface

V. Rajagopal, '~ Kvistedal, J.-H. Chung, M.P. Nash, P.M.F. Nielsen. Bioengineering Institute, University ef Auckland, Auckland, New Zealand

A number of models have been presented to describe the mechanical behavior of the skin-breast tissue interface [1]. Although models presented have been compared with clinical breast images, to our knowledge, a systematic validation of the individual modelling features has so far not been conducted. We have developed an experimental framework that allows us to test the validity of assumptions in the model by comparing predictions with experimental re- sults using materials such as silicon gels. We have validated our modelling framework for predicting surface deformations of a homogeneous silicon gel phantom [2]. The model predicted surface deformations with an RMS error of 1.8 mm for displacements in the order of 20 mm (the characteristic size of the phantom was 120 mm). We have also tracked internal markers in phantoms and are testing in a similar manner models of the skin-breast tissue inter- face. This paper presents validation results under gravity loading conditions. Experimentally, a sheet of silastic rubber is bonded to the gel phantom. The composite model tightly couples a surface membrane model to a 3D tissue model by adding the appropriate components of the stiffness matrices from the skin and adjacent tissue elements. Mechanical properties of the gel and membrane were characterized using the neo-Hookean strain energy function, with parameters estimated from independent experiments on each material. The phantom was injected with a radio-opaque liquid visible under X-ray. Motion of these internal markers were combined with surface deformations (determined using laser scanning) and compared with model predictions. The overarching aim of modelling breast biomechanics is to provide a physics- based tool for non-rigid registration of information across the various breast imaging modalities in order to aid in the localization and diagnosis of breast tumours.

References [1] N Ruiter et al. Finite element simulation of the breast's deformation during mam-

mography to generate a deformation model for registration. Bildverarbeitung fiJr die Medizin, 2003.

[2] V Rajagopal et al. Finite Element Modelling of Breast Biomechanics: Finding a Reference State. In: 26th IEEE EMBS Conference, 2004.

5682 Mo-Tu, no. 17 (P67) The molecular conformations of fibrous elastin and other proteins E.M. Green, R.E. Ellis, C.P. Winlove. University of Exeter, School efPhysics, Exeter, UK

Elastic proteins are a diverse group of extracellular matrix proteins which are widespread amongst both mammalian and non-mammalian species where they have evolved to perform varied but specific functions. All elastic proteins display the property of long-range elasticity, which is unusual amongst pro- teins whose functions generally arise from the existence of rigid secondary structures and highly ordered supramolecular assemblies. The elastic proteins are unusual in both structure and physical properties which are believed to be central to mechanical functions and also to processes including self-assembly and matrix organisation. However, the molecular and supramolecular bases of elastic protein functions are still imperfectly understood. We are addressing these questions for elastin, the principle protein of mammalian elastic tissue and for its evolutionary precursor lamprin, the principle component of the extracellular matrix in jawless agnaganths. The molecular conformation and solution dynamics of the elastin monomer and related peptides have been extensively investigated but less is known about the material in its fibrous form. In the present work we use Raman microspectrometry (model Rennishaw RM1000 equipped with a 785 nm laser) to compare ,J,- and fibrous elastin. In order to explore the molecular bases of elasticity of the fibrous material we also investigate the sensitivity of the conformation to changes in mechanical strain, temperature and swelling medium composition.

6673 Mo-Tu, no. 19 (P67) Computational model of the convection enhanced delivery of large molecules into the striatum of the adult brain

D.K. Stiles. Medtronic Neurological, Minneapolis, USA

The presence of the blood-brain barrier (BBB) frequently prevents the distri- bution of efficacious drugs to the central nervous system. To overcome this barrier, the drug can be delivered directly into the parenchyma of the brain, allowing for specific targeting of the drug to a region of interest. This approach, called convection enhanced delivery (CED), uses the distribution of velocity due to the injection from the catheter tip to spread the drug further than would be realized with simple diffusion. A computational model has been developed to help determine the specific CED distribution of an intraparenchymal delivery of a large molecule (in this case, 10,000Mr dextran) to the striatum. Using the MRI images of an adult female, a three-dimensional finite-element model (FEM) containing the caudate, putamen, internal capsule, the lateral ventricles and a spherical infusion point has been constructed. All of these structures were surrounded by a generalized white matter/grey matter brain model, to account for the diffusion of the drug into the cortex. Using clinically relevant infusion flowrates, Darcy's law and the convection/diffusion equation were solved, taking into account the anisotropy of the diffusion coefficients and hydraulic permeability in white matter, as well as the interstitial fluid clearance. The drug is modeled as chronically delivered, so both transient and steady- state effects were considered. The results of the model show the volume of distribution of the drug in the extracellular space for various catheter flowrates and concentrations.