Analogical Truth-Conditions for Metaphors

It has often been said that metaphors are based on analogies, but the nature of this relation has never been made precise. This article rigorously and formally specifies two semantic relations that do obtain between some metaphors and analogies. We argue that analogies often provide conditions of meaningfulness and truth for metaphors. An analogy is treated as an isomorphism from a source to topic domain. Metaphors are thought of as surface structures. Formal analogical conditions of meaningfulness and truth are fully and rigorously worked out for several grammatical classes of metaphors. By providing analogical meaningfulness and truth conditions for metaphors, this article shows that truth-conditional semantics can be extended to metaphors

Two-dimensional order in β-sheet peptide monolayers

Amphiphilic peptides comprising alternating hydrophilic and hydrophobic amino acid residues were designed to form super-secondary structures composed of self-assembled β-strands as monolayers at the air−water interface. Insights provided by in situ grazing-incidence X-ray diffraction (GIXD), surface pressure vs area isotherms, and Fourier transform infrared spectroscopy allow structural characterization of the assembled nanostructures and rational correlation with the peptide sequence. Peptides seven to seventeen amino acids in length were found to form crystalline arrays with coherence lengths in the range of 100 to 1000 Å. Two-dimensional registry of the self-assembled peptides was induced by placement of proline residues at the peptide termini. The films were found to intercalate ordered arrays of ions between juxtaposed β-sheet ribbons to generate peptide−ion composite phases

A designed phenylalanyl-tRNA synthetase variant allows efficient in vivo incorporation of aryl ketone functionality into proteins

Incorporation of non-natural amino acids into proteins in vivo expands the scope of protein synthesis and design. p-Acetylphenylalanine was incorporated into recombinant dihydrofolate reductase (DHFR) in Escherichia coli via a computationally designed mutant form of the phenylalanyl-tRNA synthetase of the host. DHFR outfitted with ketone functionality can be chemoselectively ligated with hydrazide reagents under mild conditions

Programmable viscoelastic matrices from artificial proteins

Extracellular matrix compliance influences cellular adhesion and migration, proliferation and apoptosis, and differentiation. Much of our current knowledge of the effects of substrate stiffness on cellular behavior is based on elastic substrates, in particular cross‐linked polyacrylamide hydrogels. Biological tissues, however, are viscoelastic and exhibit stress relaxation and energy dissipation on physiologically relevant timescales. While emerging evidence suggests that these physical properties also influence cellular behavior, materials in which viscoelasticity can be precisely engineered are currently lacking. Here, we describe programmable hydrogel matrices assembled from artificial recombinant proteins designed to be cross‐linked by covalent bonds involving cysteine residues, by association of helical domains as coiled coils, or by both mechanisms. Using these proteins, we construct chemical, physical, and chemical‐physical hydrogel networks that deform elastically or viscoelastically depending on the type of cross‐linking (Dooling et al., Adv. Mater., 2016, 28, 4651–4657). In viscoelastic networks, the amount of stress relaxation is tuned by controlling the ratio of physical cross‐linking to chemical crosslinking, and the timescale for stress relaxation is tuned over five orders of magnitude by single point mutations to the coiled‐coil physical cross‐linking domain (Dooling and Tirrell, ACS Cent. Sci., 2016, 2, 812–819). The genetic engineering approach also allows biological activity to be encoded directly within the protein sequence in the form of cell‐adhesive domains and proteolytic cleavage sites. The capacity to program the viscoelasticity and biological activity of hydrogel matrices is anticipated to have applications in studying and engineering cell‐matrix interactions

Biomimetic spatial and temporal (4D) design and fabrication

We imagine the built environment of the future as a ‘bio-hybrid machine for living in’ that will sense and react to activities within the space in order to provide experiences and services that will elevate quality of life while coexisting seamlessly with humans and the natural environment. The study of Hierarchical design in biological materials has the potential to alter the way designers/ engineers/ crafts-men of the future engage with materials in order to realise such visions. We are ex-ploring this design approach using digital manufacturing technologies such as jac-quard weaving and 3D printing

Identification of an expanded set of translationally active methionine analogues in Escherichia coli

Amino acid incorporation into proteins in vivo is controlled most stringently by the aminoacyl-tRNA synthetases. Here we report the incorporation of several new methionine analogues into protein by increasing the rate of their activation by the methionyl-tRNA synthetase (MetRS) of Escherichia coli. cis-Crotylglycine (4), 2-aminoheptanoic acid (7), norvaline (8), 2-butynylglycine (11), and allylglycine (12) will each support protein synthesis in methionine-depleted cultures of E. coli when MetRS is overexpressed and the medium is supplemented with the analogue at millimolar concentrations. These investigations suggest important opportunities for protein engineering, as expansion of the translational apparatus toward other amino acid analogues by similar strategies should also be possible

Kinetics of membrane micellization by the hydrophobic polyelectrolyte poly( 2-ethylacrylic acid)

Rates of pH-dependent micellization of multilamellar vesicles by the hydrophobic polyelectrolyte poly(2-ethylacrylic acid) (PEAA) have been measured turbidometrically. This polymer shows a strong pH-dependence in its affinity for phospholipid membranes, binding in increasing amounts as pH is lowered and ultimately solubilizing membranes to form mixed micelles (Tirrell, Takigawa and Seki (1985) Ann. N.Y. Acad. Sci. 446, 237). The rate of solubilization of dipalmitoylphosphatidylcholine (DPPC) vesicle suspensions by PEAA increases approximately linearly with reductions in pH below a threshold at pH 6.55. Interestingly, negatively-charged dipalmitoylphosphatidylglycerol membranes showed qualitatively similar behavior in the presence of PEAA, and incorporation of 10% or 20% dipalmitoylphosphatidic acid in DPPC membranes did not affect solubilization rates, demonstrating that membrane charge is not an important factor in determining micellization kinetics. Micellization of DPPC and dimyrstoylphosphatidylcholine membranes occurs most rapidly at their respective gel-liquid crystalline transition temperatures (Tm); the rate enhancement is correlated with a peak in the temperature-dependent binding of a fluorescently-modified PEAA in slightly alkaline solutions in which no micellization is observed. The lateral compressibility of the membrane, which has a similar peak at T_m, is proposed to be an important determinant of the rate and extent of polymer adsorption, and consequently of the rate of micellization

Dynamics of Phase Behavior of a Polymer Blend Under Shear Flow

We study the dynamics of the phase behavior of a polymer blend in the presence of shear flow. By adopting a two fluid picture and using a generalization of the concept of material derivative, we construct kinetic equations that describe the phase behavior of polymer blends in the presence of external flow. A phenomenological form for the shear modulus for the blend is proposed. The study indicates that a nonlinear dependence of the shear modulus of the blend on the volume fraction of one of the species is crucial for a shift in the stability line to be induced by shear flow.Comment: 16 pages, late

Toward Monodisperse Poly(γ-benzyl α,L-glutamate): Uniform, Polar, Molecular Rods

Poly(γ-benzyl α,L-glutamate) (PBLG) has been widely used in studies of the physics of rod-like polymer chains. The helical structure of PBLG gives rise to considerable chain stiffness, such that the persistence length of the chain is on the order of 70 nm in helicogenic solvents. This feature, coupled with the ease of synthesis and good solubility of the polymer has made PBLG the system of choice for the study of both isotropic and liquid crystalline solutions of rod-like macromolecules

Engineered Proteins in Materials Research

Peptides and proteins have attracted scientific and technological interest largely because of their intriguing properties as catalysts, receptors, signalling molecules, and therapeutic agents. In attempts to understand and exploit these properties, protein engineering has been used primarily to obtain precious proteins in increased quantities, or to explore systematic alterations in protein sequence through site-directed mutagenesis. Design of protein structures de novo ("from scratch") has attracted less attention, and has been directed in the main toward studies of protein folding (Kamtekar et al., 1993). Such studies represent a key element in the current vigorous investigation of the connections between amino acid sequence and the three-dimensional structures of isolated protein chains in aqueous solution. This chapter describes protein engineering of quite another sort, in which the proteinacious nature of the product is less important than its macromolecular character