Molecular Dynamics Simulations Of Lipid Membranes: The Effects Of Probes, Lipid Composition And Peptides

The cell plasma membrane is comprised of hundreds of different lipid species as well as a variety of integral and peripheral proteins. The diversity of molecular constituents leads to the formation of functional lateral heterogeneities within the plane of the membrane, known as lipid rafts, which are distinct from the surrounding membrane. Given the complexity of the plasma membrane, and the importance of rafts in the life of a cell, simplified model mixtures capturing the characteristics of the plasma membrane have been essential for unraveling its underlying behavior. In this work, we use molecular dynamics simulations to study model membranes at resolutions not possible with experimental techniques. We first investigated a fundamental assumption in model membrane experiments: that extrinsic probes added to the membrane do not disrupt membrane behavior. We addressed this issue by simulating single component model membranes that contained commonly used fluorescent lipid analogs. We found that the probes are able to disorder the bilayer and reorient lipid headgroups due to the probes' large, positively charged headgroups and long, interdigitating acyl chains. Importantly though, these effects die off within a couple of nanometers of the probe. This means that the probes do not disrupt large-scale membrane behavior and can effectively be used for experimental membrane studies. However, the short-ranged perturbations also indicate that probes may provide incorrect information if they report directly on their local, disrupted, environment. Next, we studied the behavior of more complex model membranes containing multiple lipid species. Experimentally, model membranes comprised of four lipid components can yield coexisting phases, mimicking raft and non-raft environments, ranging in size from nanometers to microns. Through simulations, we found that domain size and alignment are highly coupled and that they both change abruptly at certain lipid compositions. We also found that the phase interface between domains was only a couple of nanometers wide regardless of the properties of the two coexisting phases. Addition of transmembrane [alpha]-helical peptides of various lengths to the lipid-only mixtures significantly increased both domain size and alignment. These effects were largest for the shortest peptides and increased with peptide concentration. Thus cells may be able to control raft size and alignment, and in turn a variety of cellular processes, simply by altering lipid and protein concentrations

Integrated design : a generative multi-performative design approach

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Architecture, 2008.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.MIT Institute Archives copy: with CD-ROM; divisional library copy with no CD-ROM.Includes bibliographical references (leaves 70-72).There are building systems, called "modularized", in which the component systems (for structure, lighting, etc) can be analyzed and synthesized independently since their performance and design do not interact or affect one another. There are other building systems, called "coupled", in which the component systems do interact and influence one another. The thesis acknowledges that in a building there are both sub-systems that act independently and others that interact. While many design processes have been proposed for dealing with discrete sub-systems, there is no systematic study for building sub-systems that interrelate. This thesis examines a different design approach called integrated. The term "integrated" has a dual utilization in this study. The first use refers to the integration of form and building performance. The second use refers to the integration of interrelated and diverse building performances involving multiple disciplines. The integrated design approach analyzes and evaluates several interrelated design systems involving different disciplines in the early design phase. The goal of the approach is the generation of design alternatives guided simultaneously by two basic objectives: the aspiration for form exploration and the satisfaction of the performances of interrelated systems. After defining a framework for an integrated design approach, which includes inter-disciplinary collaboration, unified design, optimization, simulation, and other formal and digital techniques, the approach will be demonstrated in a case study. The objective of the case study is to demonstrate that the integrated design approach has validity and can be realized, in this case, for the generation of high-rise buildings guided by structural, lighting, zoning codes, and aesthetic criteria.by Eleftheria Fasoulaki.S.M

Specifying a hybrid, multiple material CAD system for next-generation prosthetic design

For many years, the biggest issue that causes discomfort and hygiene issues for patients with lower limb amputations have been the interface between body and prosthetic, the socket. Often made of an inflexible, solid polymer that does not allow the residual limb to breathe or perspire and with no consideration for the changes in size and shape of the human body caused by changes in temperature or environment, inflammation, irritation and discomfort often cause reduced usage or outright rejection of the prosthetic by the patient in their day to day lives. To address these issues and move towards a future of improved quality of life for patients who suffer amputations, Loughborough University formed the Next Generation Prosthetics research cluster. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. The research presented in this thesis is based on three primary studies. The first study involved the conception of a CAD criteria, deciding what features are needed to represent the various properties the future socket outlined by the research cluster needs. These criteria were then used for testing three CAD systems, one each from the Parametric, Non Uniform Rational Basis Spline (NURBS) and Polygon archetypes respectively. The result of these tests led to the creation of a hybrid control workflow, used as the basis for finding improvements. The second study explored emerging CAD solutions, various new systems or plug-ins that had opportunities to improve the control model. These solutions were tested individually in areas where they could improve the workflow, and the successful solutions were added to the hybrid workflow to improve and reduce the workflow further. The final study involved taking the knowledge gained from the literature and the first two studies in order to theorise how an ideal CAD system for producing future prosthetic sockets would work, with considerations for user interface issues as well as background CAD applications. The third study was then used to inform the final deliverable of this research, a software design specification that defines how the system would work. This specification was written as a challenge to the CAD community, hoping to inform and aid future advancements in CAD software. As a final stage of research validation, a number of members of the CAD community were contacted and interviewed about their feelings of the work produced and their feedback was taken in order to inform future research in this area

7th International Meshing Roundtable '98

The goal of the 7th International Meshing Roundtable is to bring together researchers and developers from industry, academia, and government labs in a stimulating, open environment for the exchange of technical information related to the meshing process. In the past, the Roundtable has enjoyed significant participation from each of these groups from a wide variety of countries

Doctor of Philosophy

dissertationVolumetric parameterization is an emerging field in computer graphics, where volumetric representations that have a semi-regular tensor-product structure are desired in applications such as three-dimensional (3D) texture mapping and physically-based simulation. At the same time, volumetric parameterization is also needed in the Isogeometric Analysis (IA) paradigm, which uses the same parametric space for representing geometry, simulation attributes and solutions. One of the main advantages of the IA framework is that the user gets feedback directly as attributes of the NURBS model representation, which can represent geometry exactly, avoiding both the need to generate a finite element mesh and the need to reverse engineer the simulation results from the finite element mesh back into the model. Research in this area has largely been concerned with issues of the quality of the analysis and simulation results assuming the existence of a high quality volumetric NURBS model that is appropriate for simulation. However, there are currently no generally applicable approaches to generating such a model or visualizing the higher order smooth isosurfaces of the simulation attributes, either as a part of current Computer Aided Design or Reverse Engineering systems and methodologies. Furthermore, even though the mesh generation pipeline is circumvented in the concept of IA, the quality of the model still significantly influences the analysis result. This work presents a pipeline to create, analyze and visualize NURBS geometries. Based on the concept of analysis-aware modeling, this work focusses in particular on methodologies to decompose a volumetric domain into simpler pieces based on appropriate midstructures by respecting other relevant interior material attributes. The domain is decomposed such that a tensor-product style parameterization can be established on the subvolumes, where the parameterization matches along subvolume boundaries. The volumetric parameterization is optimized using gradient-based nonlinear optimization algorithms and datafitting methods are introduced to fit trivariate B-splines to the parameterized subvolumes with guaranteed order of accuracy. Then, a visualization method is proposed allowing to directly inspect isosurfaces of attributes, such as the results of analysis, embedded in the NURBS geometry. Finally, the various methodologies proposed in this work are demonstrated on complex representations arising in practice and research

Fibre-reinforced additive manufacturing: from design guidelines to advanced lattice structures

In pursuit of achieving ultimate lightweight designs with additive manufacturing (AM), engineers across industries are increasingly gravitating towards composites and architected cellular solids; more precisely, fibre-reinforced polymers and functionally graded lattices (FGLs). Control over material anisotropy and the cell topology in design for AM (DfAM) offer immense scope for customising a part’s properties and for the efficient use of material. This research expands the knowledge on the design with fibre-reinforced AM (FRAM) and the elastic-plastic performance of FGLs. Novel toolpath strategies, design guidelines and assessment criteria for FRAM were developed. For this purpose, an open-source solution was proposed, successfully overcoming the limitations of commercial printers. The effect of infill patterns on structural performance, economy, and manufacturability was examined. It was demonstrated how print paths informed by stress trajectories and key geometric features can outperform conventional patterns, laying the groundwork for more sophisticated process planning. A compilation of the first comprehensive database on fibre-reinforced FGLs provided insights into the effect of grading on the elastic performance and energy absorption capability, subject to strut-and surface-based lattices, build direction and fibre volume fraction. It was elucidated how grading the unit cell density within a lattice offers the possibility of tailoring the stiffness and achieving higher energy absorption than ungraded lattices. Vice versa, grading the unit cell size of lattices yielded no effect on the performance and is thus exclusively governed by the density. These findings help exploit the lightweight potential of FGLs through better informed DfAM. A new and efficient methodology for predicting the elastic-plastic characteristics of FGLs under large strain deformation, assuming homogenised material properties, was presented. A phenomenological constitutive model that was calibrated based upon interpolated material data of uniform density lattices facilitated a computationally inexpensive simulation approach and thus helps streamline the design workflow with architected lattices.Open Acces

Design for metal fused filament fabrication (DfMF3) of Ti-6Al-4V alloy.

Additive manufacturing (AM) offers unmatchable freedom of design with the ability to manufacture parts from a wide range of materials. The technology of producing three-dimensional parts by adding material layer-by-layer has become relevant in several areas for numerous industries not only for building visual and functional prototypes but also for small and medium series production. Among others, while metal AM technologies have been established as production method, their adoption has been limited by expensive equipment, anisotropy in part properties and safety concerns related to working with loose reactive metal powder. To address this challenge, the dissertation aims at developing the fundamental understanding required to print metal parts with bound metal powder filaments using an extrusion-based AM process, known as metal fused filament fabrication (MF3). MF3 of Ti-6Al-4V has been investigated, owing to significant interest in the material from aerospace and medical industries on account of their high strength-to-weight ratio, excellent corrosion resistance and biocompatibility. To investigate the material-geometry-process interrelationship in MF3 printing, the current work looks into the process modeling and simulation, the influence of material composition and resulting characteristics on printed part properties, effects of printing parameters and slicing strategies on part quality, and part design considerations for printability. The outcome of the work is expected to provide the basis of design for MF3 (DfMF3) that is essential to unlocking the full potential of additive manufacturing. Moreover, the layer-by-layer extrusion-based printing with the highly filled material involves several challenges associated with printability, distortion and dimensional variations, residual stresses, porosity, and complexity in dealing with support structures. Currently, a high dependency on experimental trial-and-error methods to address these challenges limits the scope and efficiency of investigations. Hence, the current work presents a framework of design for MF3 and evaluates a thermo-mechanical model for finite element simulation of the MF3 printing process for virtual analyses. The capability to estimate these outcomes allows optimization of the material composition, part design, and process parameters before getting on to the physical process, reducing time and cost. The quantitative influence of material properties on MF3 printed part quality in terms of part deformation and dimensional variations was estimated using the simulation platform and results were corroborated by experiments. Also, a systematic procedure for sensitivity analysis has been presented that identified the most significant input parameters in MF3 from the material, geometry and process variables, and their relative influence on the print process outcome. Moreover, feasible geometry and process window were identified for supportless printing of Ti-6Al-4V lattice structures using the MF3 process, and an analytical approach has been presented to estimate the extrudate deflection at the unsupported overhangs in lattice structures. Finally, the design and fabrication of Ti-6Al-4V maxillofacial implants using MF3 technology are reported for the first time confirming the feasibility to manufacture patient-specific implants by MF3. The outcome of the work is an enhanced understanding of material-geometry-process interrelationships in MF3 governing DfMF3 that will enable effective design and manufacturing