Local Frustration Determines Molecular and Macroscopic Helix Structures

The effect of displaying cytochromes from an amyloid fibre is modelled as perturbation of -strands in a bilayer of helical -sheets, thereby explaining the spiral morphology of decorated amyloid and the dynamic response of morphology to cytochrome conformation. The morphology of the modelled fibre, which consists of minimal energy assemblies of rigid building blocks containing two anisotropic interacting units, depends primarily on the rigid constraints between units rather than the soft interactions between them. The framework is a discrete version of the bilayered frustration principle that drives morphology in Bauhinia seedpods. We show that self-assembly of frustrated long range structures can occur if the building blocks themselves are internally frustrated, e.g. amyloid morphology is governed by the conformation of the misfolded protein nucleating the fibre. Our model supports the idea that any peptide sequence can form amyloid if bilayers can form first, albeit stabilised by additional material such as chaperones or cytochromes. Analysis of experimentally derived amyloid structures supports our conclusions and suggests a range of frustration effects, which natural amyloid fibres may exploit. From this viewpoint, amyloid appears as a molecular example of a more general universal bilayered frustration principle, which may have profound implications for materials design using fibrous systems. Our model provides quantitative guidance for such applications. The relevance to longer length scales was proved by designing the morphology of a series of macroscopic magnetic stacks. Finally, this work leads to the idea of mixing controlled morphologically defined species to generate higher-order assembly and complex functional behaviour. The systematic kinking of decorated fibres and the nested frustration of the Bauhinia seed pod are two outstanding examples.

Electrospun fiber - Hydrogel composites for nucleus pulposus tissue engineering

New materials are needed to replace degenerated intervertebral disc tissue and to provide longer-term solutions for chronic back-pain. Replacement tissue potentially could be engineered by seeding cells into a scaffold that mimics the architecture of natural tissue. Many natural tissues, including the nucleus pulposus (the central region of the intervertebral disc) consist of collagen nanofibers embedded in a gel-like matrix. Recently it was shown that electrospun micro- or nano-fiber structures of considerable thickness can be produced by collecting fibers in an ethanol bath. Here, randomly aligned polycaprolactone electrospun fiber structures up to 50 mm thick are backfilled with alginate hydrogels to form novel composite materials that mimic the fiber-reinforced structure of the nucleus pulposus. The composites are characterized using both indentation and tensile testing. The composites are mechanically robust, exhibiting substantial strain-to-failure. The method presented here provides a way to create large biomimetic scaffolds that more closely mimic the composite structure of natural tissue. © 2012 Materials Research Society.

Generating suspended cell monolayers for mechanobiological studies.

Cell monolayers line most of the surfaces and cavities in the human body. During development and normal physiology, monolayers sustain, detect and generate mechanical stresses, yet little is known about their mechanical properties. We describe a cell culture and mechanical testing protocol for generating freely suspended cell monolayers and examining their mechanical and biological response to uniaxial stretch. Cells are cultured on temporary collagen scaffolds polymerized between two parallel glass capillaries. Once cells form a monolayer covering the collagen and the capillaries, the scaffold is removed with collagenase, leaving the monolayer suspended between the test rods. The suspended monolayers are subjected to stretching by prying the capillaries apart with a micromanipulator. The applied force can be measured for the characterization of monolayer mechanics. Monolayers can be imaged with standard optical microscopy to examine changes in cell morphology and subcellular organization concomitant with stretch. The entire preparation and testing protocol requires 3-4 d.

Award Winner in the Young Investigator Category, 2014 Society for Biomaterials Annual Meeting and Exposition, Denver, Colorado, April 16-19, 2014: Periodically perforated core-shell collagen biomaterials balance cell infiltration, bioactivity, and mechanical properties.

Orthopedic tissue engineering requires biomaterials with robust mechanics as well as adequate porosity and permeability to support cell motility, proliferation, and new extracellular matrix (ECM) synthesis. While collagen-glycosaminoglycan (CG) scaffolds have been developed for a range of tissue engineering applications, they exhibit poor mechanical properties. Building on previous work in our lab that described composite CG biomaterials containing a porous scaffold core and nonporous CG membrane shell inspired by mechanically efficient core-shell composites in nature, this study explores an approach to improve cellular infiltration and metabolic health within these core-shell composites. We use indentation analyses to demonstrate that CG membranes, while less permeable than porous CG scaffolds, show similar permeability to dense materials such as small intestine submucosa (SIS). We also describe a simple method to fabricate CG membranes with organized arrays of microscale perforations. We demonstrate that perforated membranes support improved tenocyte migration into CG scaffolds, and that migration is enhanced by platelet-derived growth factor BB-mediated chemotaxis. CG core-shell composites fabricated with perforated membranes display scaffold-membrane integration with significantly improved tensile properties compared to scaffolds without membrane shells. Finally, we show that perforated membrane-scaffold composites support sustained tenocyte metabolic activity as well as improved cell infiltration and reduced expression of hypoxia-inducible factor 1α compared to composites with nonperforated membranes. These results will guide the design of improved biomaterials for tendon repair that are mechanically competent while also supporting infiltration of exogenous cells and other extrinsic mediators of wound healing.

MRI features of cellular angiomyofibroma with pathologic correlation.

Within the spectrum of extratesticular mesenchymal tumors in the scrotum and perineum lies cellular angiofibroma, also known as angiomyofibroblastoma-like tumor, a rare lesion originally described to almost exclusively occur in the vulva, perineum, and pelvis of women. We report a case of this tumor, with an adjacent scrotal lipoma, occurring in a 60-year-old male who presented to our department with a firm palpable scrotal mass. To our knowledge, the MRI findings of this entity have yet to be described in the radiological literature. We present the MRI features of cellular angiofibroma that are consistent with the pathological characteristics of this entity-a benign cellular and fibrous tumor with prominent vascularity.

Mechanical behaviour of electrospun fibre-reinforced hydrogels.

Mechanically robust and biomimicking scaffolds are needed for structural engineering of tissues such as the intervertebral disc, which are prone to failure and incapable of natural healing. Here, the formation of thick, randomly aligned polycaprolactone electrospun fibre structures infiltrated with alginate is reported. The composites are characterised using both indentation and tensile testing and demonstrate substantially different tensile and compressive moduli. The composites are mechanically robust and exhibit large strains-to-failure, exhibiting toughening mechanisms observed in other composite material systems. The method presented here provides a way to create large-scale biomimetic scaffolds that more closely mimic the composite structure of natural tissue, with tuneable tensile and compressive properties via the fibre and matrix phases, respectively.

Time-dependent fracture toughness of cornea.

The fracture and time-dependent properties of cornea are very important for the development of corneal scaffolds and prostheses. However, there has been no systematic study of cornea fracture; time-dependent behavior of cornea has never been investigated in a fracture context. In this work, fracture toughness of cornea was characterized by trouser tear tests, and time-dependent properties of cornea were examined by stress-relaxation and uniaxial tensile tests. Control experiments were performed on a photoelastic rubber sheet. Corneal fracture resistance was found to be strain-rate dependent, with values ranging from 3.39±0.57 to 5.40±0.48kJm(-2) over strain rates from 3 to 300mmmin(-1). Results from stress-relaxation tests confirmed that cornea is a nonlinear viscoelastic material. The cornea behaved closer to a viscous fluid at small strain but became relatively more elastic at larger strain. Although cornea properties are greatly dependent on time, the stress-strain responses of cornea were found to be insensitive to the strain rate when subjected to tensile loading.

Mechanics of biological networks: from the cell cytoskeleton to connective tissue.

From the cell cytoskeleton to connective tissues, fibrous networks are ubiquitous in metazoan life as the key promoters of mechanical strength, support and integrity. In recent decades, the application of physics to biological systems has made substantial strides in elucidating the striking mechanical phenomena observed in such networks, explaining strain stiffening, power law rheology and cytoskeletal fluidisation - all key to the biological function of individual cells and tissues. In this review we focus on the current progress in the field, with a primer into the basic physics of individual filaments and the networks they form. This is followed by a discussion of biological networks in the context of a broad spread of recent in vitro and in vivo experiments.

Mechanical behaviour of electrospun fibre-reinforced hydrogels

Mechanically robust and biomimicking scaffolds are needed for structural engineering of tissues such as the intervertebral disc, which are prone to failure and incapable of natural healing. Here, the formation of thick, randomly aligned polycaprolactone electrospun fibre structures infiltrated with alginate is reported. The composites are characterised using both indentation and tensile testing and demonstrate substantially different tensile and compressive moduli. The composites are mechanically robust and exhibit large strains-to-failure, exhibiting toughening mechanisms observed in other composite material systems. The method presented here provides a way to create large-scale biomimetic scaffolds that more closely mimic the composite structure of natural tissue, with tuneable tensile and compressive properties via the fibre and matrix phases, respectively. © 2014 Springer Science+Business Media New York.

Rapid patterning of 1-D collagenous topography as an ECM protein fibril platform for image cytometry.

Cellular behavior is strongly influenced by the architecture and pattern of its interfacing extracellular matrix (ECM). For an artificial culture system which could eventually benefit the translation of scientific findings into therapeutic development, the system should capture the key characteristics of a physiological microenvironment. At the same time, it should also enable standardized, high throughput data acquisition. Since an ECM is composed of different fibrous proteins, studying cellular interaction with individual fibrils will be of physiological relevance. In this study, we employ near-field electrospinning to create ordered patterns of collagenous fibrils of gelatin, based on an acetic acid and ethyl acetate aqueous co-solvent system. Tunable conformations of micro-fibrils were directly deposited onto soft polymeric substrates in a single step. We observe that global topographical features of straight lines, beads-on-strings, and curls are dictated by solution conductivity; whereas the finer details such as the fiber cross-sectional profile are tuned by solution viscosity. Using these fibril constructs as cellular assays, we study EA.hy926 endothelial cells' response to ROCK inhibition, because of ROCK's key role in the regulation of cell shape. The fibril array was shown to modulate the cellular morphology towards a pre-capillary cord-like phenotype, which was otherwise not observed on a flat 2-D substrate. Further facilitated by quantitative analysis of morphological parameters, the fibril platform also provides better dissection in the cells' response to a H1152 ROCK inhibitor. In conclusion, the near-field electrospun fibril constructs provide a more physiologically-relevant platform compared to a featureless 2-D surface, and simultaneously permit statistical single-cell image cytometry using conventional microscopy systems. The patterning approach described here is also expected to form the basics for depositing other protein fibrils, seen among potential applications as culture platforms for drug screening.

日本血吸虫三链形成寡核苷酸结合位点的全基因组分析及其应用探讨

血吸虫病是一种广泛分布于亚、非、拉美州的寄生虫病，威胁着成千上万人的健康安全。然而，目前血吸虫病防治面临着一系列的挑战。 “三链形成寡核苷酸（TFO）”能位点特异性地结合双链DNA，已被用于抑制基因的转录表达、介导DNA突变和目标基因的敲除、诱导DNA重组及介导双链DNA的位点特异性切割等。因而该技术对于血吸虫的功能基因组学研究和血吸虫病的防治具有重要的应用前景。由于高亲和性、特异的TFO结合位点是该技术发挥作用的先决条件，因而想要实现该应用，就必须首先了解血吸虫基因组中的“三链形成寡核苷酸结合位点（TTS）”的分布、含量情况以及分析它们作为有效作用靶点的可能性。 本研究通过对日本血吸虫全基因组的搜索与分析，发现该基因组中基因的上游序列（起始密码子到上游1500bp间）较之转录区及整个基因组中的平均水平具有更高的TTS含量，且长TTS含量也更高。并鉴定出共有7576个基因可以在scaffolds数据中提取出基因区（上游序列+基因转录区），其中98%都含有至少1个高亲和性的TTS。在这些基因中鉴定出了5177个只在某一基因中独有的TTS，同时反之也鉴定出了2878个含有至少1个这种独有TTS的基因，其中包括25个编码代谢途径关键酶的基因和231个在人类基因组中没有同源基因且暂无功能注释的基因，这些基因均可能成为药物的作用靶标。此外，还鉴定出了5689个人类基因组中所没有而日本血吸虫具有的TTS，其中有1013个出现于日本血吸虫的基因区。这些TTS有可能为各种基于TFO技术的基因打靶，或直接利用TFO技术设计抗血吸虫药物提供特异的靶位点。因此，本研究揭示出了日本血吸虫基因组中存在着丰富的高亲和性和特异的三螺旋形成位点，提示TFO技术可以作为血吸虫功能基因组学研究的潜在重要手段。同时，该技术也可为血吸虫病的防治提供了一条重要的途径。

Fruit anatomy,seed germination and seedling development in the Japanese seagrass phyllospadix

Phyllospadix iwatensis Makino and phyllospadix japonicus Makino have similar frunt morphology and anatomy.The rhomboid fruit of Japanese phyllospadix is dark brown in colour and is characterized by two arms bearing stiff inflected bristles which can act as an anchoring system. The fruit covering consists of a thin cuticular seed coat and pericarp remains mainly fibrous endocarp. In the groove region of the fruit.the cuticular seed coat and endocarp are replaced by nucellus cells with wall in growths and crushed pigment strands with lignified walls.these tissues appera to control the transfer of nutrients to developing seed.the seed is oval with a small embryo and a large hypocotyl. the embryo is straight and simple,with the plumule containing three leaf primordia and a pair of root primordia surrounded by a cotyledon.the hypocotyl has large vontral lobe containing central provascular tissue and two small dorsal lobes.the hypocotyl contains starch.lipid and protein.and acts as a nutrient store.the seed of P.iwatensis has a dormancy period of 2-6 weeks and germination eventually reaches-65%.but is not synchronized.during germination the leaves emerge first.and then after at least three young leaves have formed and abseised.the roots emerge,usually?6 months after the commencement of germination.Utilizaton of the nutrient reserves is initially from the perihpery of the hypocotyl and then progressively towards its centre.

赤霉素、硫脲处理对黄精根状茎和须根发生的影响

为诱导无芽黄精根状茎产生不定芽,选择不同的化学物质进行诱导处理。结果表明,GA3处理效果明显,选用0.4 mg/L的GA3浸泡25 min对黄精根状茎不定芽的产生和须根生长有明显促进作用,高浓度抑制其生长;1%硫脲浸泡处理对黄精无顶芽根状茎萌发新芽和须根有明显的抑制作用。

A solid-state dye-sensitized solar cell based on a novel ionic liquid gel and ZnO nanoparticles on a flexible polymer substrate

This paper describes a new strategy to make a full solid-state, flexible, dye-sensitized solar cell (DSSC) based on novel ionic liquid gel, organic dye, ZnO nanoparticles and carbon nanotube (CNT) thin film stamped onto a polyethylene terephthalate (PET) substrate. The CNTs serve both as the charge collector and as scaffolds for the growth of ZnO nanoparticles, where the black dye molecules are anchored.

Surface modification of bioactive glass nanoparticles and the mechanical and biological properties of poly(L-lactide) composites

Novel bioactive glass (13G) nanoparticles/poly(L-lactide) (PLLA) composites were prepared as promising bone-repairing materials. The BG nanoparticles (Si:P:Ca = 29:13:58 weight ratio) of about 40 run diameter were prepared via the sol-gel method. In order to improve the phase compatibility between the polymer and the inorganic phase, PLLA (M-n = 9700 Da) was linked to the surface of the BG particles by diisocyanate. The grafting ratio of PLLA was in the vicinity of 20 wt.%. The grafting modification could improve the tensile strength, tensile modulus and impact energy of the composites by increasing the phase compatibility.