Stability of domain structures in multi-domain proteins

Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR.

Simultaneous Geometry Optimization and Material Selection for Truss Structures

In this work, we explore simultaneous design and material selection by posing it as an optimization problem. The underlying principles for our approach are Ashby's material selection procedure and structural optimization. For the simplicity and ease of initial implementation of the general procedure, truss structures under static load are considered in this work in view of maximum stiffness, minimum weight/cost and safety against failure. Along the lines of Ashby's material indices, a new design index is derived for trusses. This helps in choosing the most suitable material for any design of a truss. Using this, both the design space and material database are searched simultaneously using optimization algorithms. The important feature of our approach is that the formulated optimization problem is continuous even though the material selection is an inherently discrete problem.

Topology Optimization of Micromachined Structures with Surface Micromachining Manufacturing Constraints

Topology optimization methods have been shown to have extensive application in the design of microsystems. However, their utility in practical situations is restricted to predominantly planar configurations due to the limitations of most microfabrication techniques in realizing structures with arbitrary topologies in the direction perpendicular to the substrate. This study addresses the problem of synthesizing optimal topologies in the out-of-plane direction while obeying the constraints imposed by surface micromachining. A new formulation that achieves this by defining a design space that implicitly obeys the manufacturing constraints with a continuous design parameterization is presented in this paper. This is in contrast to including manufacturing cost in the objective function or constraints. The resulting solutions of the new formulation obtained with gradient-based optimization directly provide the photolithographic mask layouts. Two examples that illustrate the approach for the case of stiff structures are included.

Topology Optimization of Electrostatically Actuated Micromechanical Structures with Accurate Electrostatic Modeling of the Interpolated Material Model

In this paper, we present a novel formulation for performing topology optimization of electrostatically actuated constrained elastic structures. We propose a new electrostatic-elastic formulation that uses the leaky capacitor model and material interpolation to define the material state at every point of a given design domain continuously between conductor and void states. The new formulation accurately captures the physical behavior when the material in between a conductor and a void is present during the iterative process of topology optimization. The method then uses the optimality criteria method to solve the optimization problem by iteratively pushing the state of the domain towards that of a conductor or a void in the appropriate regions. We present examples to illustrate the ability of the method in creating the stiffest structure under electrostatic force for different boundary conditions.

Measurement of Stress-Strain Response of A Rammed Earth Prism In Compression Using Fiber Bragg Grating Sensors

A comparative study of strain response and mechanical properties of rammed earth prisms, has been made using Fiber Bragg Grating (FBG) sensors (optical) and clip-on extensometer (electro-mechanical). The aim of this study is to address the merits and demerits of traditional extensometer vis-à-vis FBG sensor; a uni-axial compression test has been performed on a rammed earth prism to validate its structural properties from the stress - strain curves obtained by two different methods of measurement. An array of FBG sensors on a single fiber with varying Bragg wavelengths (..B), has been used to spatially resolve the strains along the height of the specimen. It is interesting to note from the obtained stress-strain curves that the initial tangent modulus obtained using the FBG sensor is lower compared to that obtained using clip-on extensometer. The results also indicate that the strains measured by both FBG and extensometer sensor follow the same trend and both the sensors register the maximum strain value at the same time.

The determination of stem cell fate by 3D scaffold structures through the control of cell shape

Stem cell response to a library of scaffolds with varied 3D structures was investigated. Microarray screening revealed that each type of scaffold structure induced a unique gene expression signature in primary human bone marrow stromal cells (hBMSCs). Hierarchical cluster analysis showed that treatments sorted by scaffold structure and not by polymer chemistry suggesting that scaffold structure was more influential than scaffold composition. Further, the effects of scaffold structure on hBMSC function were mediated by cell shape. Of all the scaffolds tested, only scaffolds with a nanofibrous morphology were able to drive the hBMSCs down an osteogenic lineage in the absence of osteogenic supplements. Nanofiber scaffolds forced the hBMSCs to assume an elongated, highly branched morphology. This same morphology was seen in osteogenic controls where hBMSCs were cultured on flat polymer films in the presence of osteogenic supplements (OS). In contrast, hBMSCs cultured on flat polymer films in the absence of OS assumed a more rounded and less-branched morphology. These results indicate that cells are more sensitive to scaffold structure than previously appreciated and suggest that scaffold efficacy can be optimized by tailoring the scaffold structure to force cells into morphologies that direct them to differentiate down the desired lineage. Published by Elsevier Ltd.

Synthesis and Characterization of Carbon Nanotube-Polymer Multilayer Structures

We develop lightweight, multilayer materials composed of alternating layers of poly dimethyl siloxane (PDMS) polymer and vertically aligned carbon nanotube (CNT) arrays, and characterize their mechanical response in compression. The CNT arrays used In the assembly are synthesized with graded mechanical properties along their thickness, and their use enables the creation of multilayer structures with low density (0.12-0.28 g/cm(3)). We test the mechanical response of structures composed of different numbers of CNT layers partially embedded in PDMS polymer, under quasi-static and dynamic loading. The resulting materials exhibit a hierarchical, fibrous structure with unique mechanical properties: They can sustain large compressive deformations (up to similar to 0.8 strain) with a nearly complete recovery and present strain localization in selected sections of the materials. Energy absorption, as determined by the hysteresis observed In stress-strain curves, is found to be at least 3 orders of magnitude larger than that of natural and synthetic cellular materials of comparable density. Conductive bucky paper Is Included within the polymer interlayers. This allows the measurement of resistance variation as a function of applied stress, showing strong correlation with the observed strain localization In compression.