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Nature has been developing adhesives for millions of years, mankind for just a few thousands of years. For this reason it is worth having a closer look at what nature does and how we can develop bio-inspired adhesives for technical and medical applications. Some examples of natural materials which have already been used for technical adhesives are casein, latex rubber, tree gum, and adhesives derived from natural sources used for the waterproofing of natural textiles, the production of paper, and the sealing of jars (Papov et al., 1995; Creton and Papon, 2003). Bio-inspired adhesives can be found in all areas of the natural world. Because of their origin, those adhesives are also called biological adhesives or bioadhesives and they fulfill several different functions (Smith and Callow, 2006; Carrington, 2008; Antonietti and Fratzl, 2010). Plants use adhesives, for example, for self-healing and for protecting themselves against wood defects, while animals use sticky materials for protecting themselves against predators and for hunting prey (Keckes et al., 2003; Schreiber et al., 2005; Flammang, 2006; Voigt and Gorb, 2008; Plaza et al., 2009). Microorganisms use adhesive material for settlement, surface attachment, and colonization (Melzer et al., 2008; Flammang et al., 2009; Santos et al., 2009; Scholz et al., 2009). Higher organisms, such as humans, rely on an inducible adhesive system: the wound healing promoter fibrinogen ((Berlind et al., 2010), which is discussed in detail in Chapter 15, p. 225 of this book).

In an attempt to improve TRAIL's (tumor necrosis factor-related apoptosis-inducing ligand) tumor selective activity a variant was designed, in which the three TRAIL protomers are expressed as a single polypeptide chain (scTRAIL). By genetic fusion with a single-chain antibody fragment (scFv) recognizing the extracellular domain of ErbB2, we further equipped scTRAIL with tumor-targeting properties. We studied tumor targeting and apoptosis induction of scFv-scTRAIL in comparison with non-targeted scTRAIL. Importantly, the tumor antigen-targeted scTRAIL fusion protein showed higher apoptotic activity in vitro, with a predominant action by TRAIL-R2 signaling. Pharmacokinetic studies revealed increased plasma half-life of the targeted scTRAIL fusion protein compared with scTRAIL. In vivo studies in a mouse tumor model with xenotransplanted Colo205 cells confirmed greater response to the ErbB2-specific scTRAIL fusion protein compared with non-targeted scTRAIL both under local and systemic application regimen. Together, in vitro and in vivo data give proof of concept of higher therapeutic activity of tumor-targeted scFv-scTRAIL molecules. Further, we envisage that through targeting of scTRAIL, potential side effects should be minimized. We propose that scFv-mediated tumor targeting of single-chain TRAIL represents a promising strategy to improve TRAIL's antitumoral action and to minimize potential unwanted actions on normal tissues.Cell Death and Disease (2010) 1, e68; doi:10.1038/cddis.2010.45; published online 26 August 2010.

The biopolymer chitosan has shown great potential for a tremendous number of applications despite the fact that typical chitosan preparations are always mixtures of different chemical entities, natural impurities and process-induced impurities. However, chitosan preparations described in the literature or offered on the market are analytically highly undefined. Here we propose a T-SAR (thinking in terms of structure-activity-relationships) guided multi-dimensional analysis of distinct chitosan preparations with the aim a) to obtain the information needed for the production of reproducible chitosan preparations and b) to predict biological effects and technological properties of certain chitosan preparations. First, a physico-chemical description (molecular weight (M-W), polydispersity (M-W/M-N), fraction of acetylation (F-A), pattern of acetylation (P-A), hydrodynamic radius (R-h), intrinsic viscosity ([eta])) of six selected samples was done. Furthermore chitosan properties like solubility, crystallinity, conformation (Mark-Houwink-plot) and impurities of all the chitosan preparations from different origins were determined and biological effects were also analyzed using test systems with two different bacteria (Escherichia coli, Vibrio fischeri). It was found that the presence of HCl enabled the water solubility of chitosan, while chloride-free chitosan was only soluble in acetic acid. The pattern of acetylation P-A showed no impact on this behavior. The analyzed biological effects revealed growth inhibition within 30 minutes for E. coli and a decreased bioluminescence for V. fisheri (IC50 = 0.035 w%). Thus, the strategy to check biological effects within a multi-dimensional analysis kit proved to be effective for detecting general structure-property-relationships of chitosan in relation to its biological effects.

A plant lectin was isolated from barley (Hordeum vulgare) coleoptiles using acidic extraction and different chromatographic methods. Sequencing of more than 50% of the protein sequence by Edman degradation confirmed a full-length cDNA clone. The subsequently identified open reading frame encodes for a 15 kDa protein which could be found in the soluble fraction of barley coleoptiles. This protein exhibited specificity towards mannose sugar and is therefore, accordingly named as Horcolin (Hordeum vulgare coleoptile lectin). Database searches performed with the Horcolin protein sequence revealed a sequence and structure homology to the lectin family of jacalin-related lectins. Together with its affinity towards mannose, Horcolin is now identified as a new member of the mannose specific subgroup of jacalin-related lectins in monocot species. Horcolin shares a high amino acid homology to the highly light-inducible protein HL#2 and, in addition to two methyl jasmonic acid-inducible proteins of 32.6 and 32.7 kDa where the jasmonic acid-inducible proteins are examples of bitopic chimerolectins containing a dirigent and jacalin-related domain. Immunoblot analysis with a cross-reactive anti-HL#2 antibody in combination with Northern blot analysis of the Horcolin cDNA revealed tissue specific expression of Horcolin in the coleoptiles. The function of Horcolin is discussed in the context of its particular expression in coleoptiles and is then compared to other lectins, which apparently share a related response to biotic or abiotic stress factors.

Most members of the tumor necrosis factor (TNF) ligand family occur in both a membrane-bound and a soluble form, which can possess differential bioactivities. The aim of this work was the construction of a synthetic-biological hybrid system consisting of chemically nanostructured core-shell particles with a diameter of 100 nm, 1 microm, or 10 microm and the cytokine TNF to obtain a tool that mimics the bioactivity of naturally occurring membrane-bound TNF. Synthetic core-shell nanoparticles consisting of an inorganic silica core and an ultrathin organic shell bearing a maleimide group at the shell surface which allowed for a covalent and site-directed coupling of CysHisTNF mutants were prepared. The TNF mutants were modified at the N-terminus by PCR cloning by introducing a His-Tag for purification and a free cysteine group for reaction with the particle-attached maleimide group. The resulting nanostructured hybrid particles initiated strong TNF receptor type 2 specific responses, otherwise only seen for the membrane-bound form of TNF, but not the soluble cytokine, thus clearly demonstrating new and membrane TNF-like properties of the bioconjugated soluble TNF.

Magnetic iron oxide nanoparticles (Fe-NP) are currently considered for various diagnostic and therapeutic applications in the brain. However, little is known on the accumulation and biocompatibility of such particles in brain cells. We have synthesized and characterized dimercaptosuccinic acid (DMSA) coated Fe-NP and have investigated their uptake by cultured brain astrocytes. DMSA-coated Fe-NP that were dispersed in physiological medium had an average hydrodynamic diameter of about 60 nm. Incubation of cultured astrocytes with these Fe-NP caused a time- and concentration-dependent accumulation of cellular iron, but did not lead within 6 h to any cell toxicity. After 4 h of incubation with 100–4000 µM iron supplied as Fe-NP, the cellular iron content reached levels between 200 and 2000 nmol mg − 1 protein. The cellular iron content after exposure of astrocytes to Fe-NP at 4 °C was drastically lowered compared to cells that had been incubated at 37 °C. Electron microscopy revealed the presence of Fe-NP-containing vesicles in cells that were incubated with Fe-NP at 37 °C, but not in cells exposed to the nanoparticles at 4 °C. These data demonstrate that cultured astrocytes efficiently take up DMSA-coated Fe-NP in a process that appears to be saturable and strongly depends on the incubation temperature.