Paper “Osteoconductivity of silk calcified organic-inorganic interfaces.”

In preparation. 

 

Paper "Design and characterization of a novel silk-elastin graphene composite for controlled electrical outcomes".

In preparation. 

 

Paper “Processing Silk with High Pressure and Heat”.

In preparation. 

 

Paper “Mechanics of mineralized collagen fibrils upon transient loads”, 2020

ACS Nano. Submitted. 

 

Paper “Viscoelasticity in mineralized collagen fibrils.” 2020

In preparation.

 

Paper “Size effects of silk-silica biomineralized nanoparticles in osteogenesis.”

In preparation.

 

Paper “Molecular dynamics methods for the prediction of osteogenesis potential in biomineralized silk-based biomaterials.”

In preparation.

 

Paper "Study of the interaction between silk fibroin and hydroxyapatite for bone regeneration application"

In preparation

 

Paper “Charge-modulated activity of a tyrosine containing SELP.”

In preparation. 

 

Paper “ColGen: A Generative model using Artificial Intelligence to Generate de novo Thermally Stable Collagen Sequences.”

In preparation.

 

Paper "Deep Learning to Generate Thermally Stable Collagen Sequences with Molecular Simulations and Experimental Examination.”

In preparation.
 

 

Model credibility assessment

Click here. 

 

Method paper on Collagen, published in ACS Biomaterials Science & Engineering, Jan 2020

ACS Biomater. Sci. Eng. XXXX, XXX, XXX−XXX

DOI: 10.1021/acsbiomaterials.9b01742

Abstract: Collagen is the key protein of connective tissue (i.e., skin, tendons and ligaments, and cartilage, among others), accounting for 25–35% of the whole-body protein content and conferring mechanical stability. This protein is also a fundamental building block of bone because of its excellent mechanical properties together with carbonated hydroxyapatite minerals. Although the mechanical resilience and viscoelasticity have been studied both in vitro and in vivo from the molecular to tissue level, wave propagation properties and energy dissipation have not yet been deeply explored, in spite of being crucial to understanding the vibration dynamics of collagenous structures (e.g., eardrum, cochlear membranes) upon impulsive loads. By using a bottom-up atomistic modeling approach, here we study a collagen peptide under two distinct impulsive displacement loads, including longitudinal and transversal inputs. Using a one-dimensional string model as a model system, we investigate the roles of hydration and load direction on wave propagation along the collagen peptide and the related energy dissipation. We find that wave transmission and energy-dissipation strongly depend on the loading direction. Also, the hydrated collagen peptide can dissipate five times more energy than dehydrated one. Our work suggests a distinct role of collagen in term of wave transmission of different tissues such as tendon and eardrum. This study can step toward understanding the mechanical behavior of collagen upon transient loads, impact loading and fatigue, and designing biomimetic and bioinspired materials to replace specific native tissues such as the tympanic membrane. 

 

Method paper on ossicular replacement prostheses, published in Journal of the Mechanical Behavior of Biomedical Materials, Nov 2019

J Mech Behav Biomed, 2020, 103, 103541

DOI: 10.1016/j.jmbbm.2019.103541.

Abstract: Conductive hearing loss, due to middle ear pathologies or traumas, affects more than 5% of the population worldwide. Passive prostheses to replace the ossicular chain mainly rely on piston-like titanium and/or hydroxyapatite devices, which in the long term suffer from extrusion. Although the basic shape of such devices always consists of a base for contact with the eardrum and a stem to have mechanical connection with the residual bony structures, a plethora of topologies have been proposed, mainly to help surgical positioning. In this work, we optimize the topology of a total ossicular replacement prosthesis, by maximizing the global stiffness and under the smallest possible volume constraint that ensures material continuity. This investigation optimizes the prosthesis topology in response to static displacement loads with amplitudes that normally occur during sound stimulation in a frequency range between 100 Hz and 10 kHz. Following earlier studies, we discuss how the presence and arrangement of holes on the surface of the prosthesis plate in contact with the umbo affect the overall geometry. Finally, we validate the designs through a finite-element model, in which we assess the prosthesis performance upon dynamic sound pressure loads by considering four different constitutive materials: titanium, cortical bone, silk, and collagen/hydroxyapatite. The results show that the selected prostheses present, almost independently of their constitutive material, a vibroacustic behavior close to that of the native ossicular chain, with a slight almost constant positive shift that reaches a maximum of �5 dB close to 1 kHz. This work represents a reference for the development of a new generation of middle ear prostheses with non-conventional topologies for fabrication via additive manufacturing technologies or ultraprecision machining in order to create patient-specific devices to recover from conductive hearing loss.

 

Method paper on human enamel, published in Nature Communications, Sep 2019

Nat Commun 2019, 10, 4383

DOI: 10.1038/s41467-019-12185-7

Abstract: Enamel is the hardest and most resilient tissue in the human body. Enamel includes morphologically aligned, parallel, ∼50 nm wide, microns-long nanocrystals, bundled either into 5-μm-wide rods or their space-filling interrod. The  orientation of enamel crystals, however, is poorly understood. Here we show that the crystalline c-axes are homogenously oriented in interrod crystals across most of the enamel layer thickness. Within each rod crystals are not co-oriented with one another or with the long axis of the rod, as previously assumed: the c-axes of adjacent nanocrystals are most frequently mis-oriented by 1°–30°, and this orientation within each rod gradually changes, with an overall angle spread that is never zero, but varies between 30°–90° within one rod. Molecular dynamics simulations demonstrate that the observed mis-orientations of adjacent crystals induce crack deflection. This toughening mechanism contributes to the unique resilience of enamel, which lasts a lifetime under extreme physical and chemical challenges. 

 

Method paper on Conductive Silk-Based Composites, published in Advanced Materials, Sep 2019

Adv. Mater. 2019, 31, 1904720

DOI: 10.1002/adma.201904720

Abstract: There is great interest in developing conductive biomaterials for the manufacturing of sensors or flexible electronics with applications in healthcare, tracking human motion, or in situ strain measurements. These biomaterials aim to overcome the mismatch in mechanical properties at the interface between typical rigid semiconductor sensors and soft, often uneven biological surfaces or tissues for in vivo and ex vivo applications. Here, the use of biobased carbons to fabricate conductive, highly stretchable, flexible, and biocompatible silk-based composite biomaterials is demonstrated. Biobased carbons are synthesized via hydrothermal processing, an aqueous thermochemical method that converts biomass into a carbonaceous material that can be applied upon activation as conductive filler in composite biomaterials. Experimental synthesis and full-atomistic molecular dynamics modeling are combined to synthesize and characterize these conductive composite biomaterials, made entirely from renewable sources and with promising applications in fields like biomedicine, energy, and electronics.

 

Review paper on Hydroxyapatite-Reinforced Composites, published in Advanced Functional Materials, Jul 2019

Adv. Funct. Mater. 2019, 29, 1903055

DOI: 10.1002/adfm.201903055

Abstract: Additive manufacturing (AM) techniques have gained interest in the tissue engineering field, thanks to their versatility and unique possibilities of producing constructs with complex macroscopic geometries and defined patterns. Recently, composite materials—namely, heterogeneous biomaterials identified as continuous phase (matrix) and reinforcement (filler)—have been proposed as inks that can be processed by AM to obtain scaffolds with improved biomimetic and bioactive properties. Significant efforts have been dedicated to
hydroxyapatite (HA)-reinforced composites, especially targeting bone tissue engineering, thanks to the chemical similarities of HA with respect to mineral components of native mineralized tissues. Herein, applications of AM techniques to process HA-reinforced composites and biocomposites for the production of scaffolds with biological matrices, including cellular tissues, are reviewed. The primary outcomes of recent investigations in terms of morphological, structural, and in vitro and in vivo biological properties of the materials are discussed. The approaches based on the nature of the matrices employed to embed the HA reinforcements and produce the tissue substitutes are classified, and a critical discussion is provided on the presented state of the art as well as the future perspectives, to offer a omprehensive picture of the strategies investigated as well as challenges in this emerging field of materiomics.

 

Paper on Dynamic pigmentary and structural coloration within cephalopod chromatophore organs, published in Nature Communications, Mar 2019

Nat Commun 2019, 10, 1004.

DOI: 10.1038/s41467-019-08891-x

Abstract: Chromatophore organs in cephalopod skin are known to produce ultra-fast changes in appearance for camouflage and communication. Light-scattering pigment granules within chromatocytes have been presumed to be the sole source of coloration in these complex organs. We report the discovery of structural coloration emanating in precise register with expanded pigmented chromatocytes. Concurrently, using an annotated squid chromatophore proteome together with microscopy, we identify a likely biochemical component of this reflective coloration as reflectin proteins distributed in sheath cells that envelop each chromatocyte. Additionally, within the chromatocytes, where the pigment resides in nanostructured granules, we find the lens protein Ω- crystallin interfacing tightly with pigment
molecules. These findings offer fresh perspectives on the intricate biophotonic interplay between pigmentary and structural coloration elements tightly co-located within the same dynamic flexible organ - a feature that may help inspire the development of new classes of
engineered materials that change color and pattern. 

 

Method paper on Graphyne-Based Materials, published in Advanced Materials, Jan 2019

Adv. Mater. 2019, 31, 1805665

DOI: 10.1002/adma.201805665.

Abstract: By varying the number of acetylenic linkages connecting aromatic rings, a new family o f atomically thin graph-n-yne materials can be designed and synthesized. Generating immense scientific interest due to its structural diversity and excellent physical properties, graph-n-yne has opened new avenues toward numerous promising engineering applications, especially for separation membranes with precise pore sizes. Having these tunable pore sizes in combination with their excellent mechanical strength to withstand high pressures,
free-standing graph-n-yne is theoretically posited to be an outstanding membrane material for separating or purifying mixtures of either gases or liquids, rivaling or even dramatically exceeding the capabilities of current, state-of-art separation membranes. Computational modeling and simulations play an integral role in the bottom-up design and characterization of these graph-n-yne materials. Thus, here, the state of the art in modeling α-, β-, γ-, δ-, and 6,6,12-graphyne nanosheets for synthesizing graph-2-yne materials and 3D architectures thereof is discussed. Different synthesis methods are described and a broad overview of computational characterizations of graphn-
yne’s electrical, chemical, and thermal properties is provided. Furthermore, a series of in-depth computational studies that delve into the specifics of graph-n-yne’s mechanical strength and porosity, which confer superior performance for separation and desalination membranes, are reviewed.

 

Review paper on Multiscale Modeling of Silk and Silk-Based Biomaterials, published in Macromolecular Bioscience, Oct 2018

Macromol. Biosci. 2019, 19, 1800253

DOI: 10.1002/mabi.201800253.

Abstract: Silk embodies outstanding material properties and biologically relevant functions achieved through a delicate hierarchical structure. It can be used to create high-performance, multifunctional, and biocompatible materials through mild processes and careful rational material designs. To achieve this goal, computational modeling has proven to be a powerful platform to unravel the causes of the excellent mechanical properties of silk, to predict the properties of the biomaterials derived thereof, and to assist in devising new manufacturing strategies. Fine-scale modeling has been done mainly through all-atom and coarse-grained molecular dynamics simulations, which offer a bottom-up description of silk. In this work, a selection of relevant contributions of computational modeling is reviewed to understand the properties of natural silk, and to the design of silk-based materials, especially combined with experimental methods. Future research directions are also pointed out, including approaches such as 3D printing and machine learning, that may enable a high throughput design and manufacturing of silk-based biomaterials.

 

SITEP Tutorial Video submitted for the IMAG video competition, September 2018: https://vimeo.com/285941736 (awarded 3rd prize in the MSM consortium meeting, March 2019)

 

Tutorial Paper on Silkworm Silk-based biomaterials published in Chemical Society Reviews, June 2018

Chem. Soc. Rev., 2018, 47, 6486-6504

DOI: 10.1039/C8CS00187A

Silks are natural fibrous protein polymers that are spun by silkworms and spiders. Among silk variants, there has been increasing interest devoted to the silkworm silk of B. mori, due to its availability in large quantities along with its unique material properties. Silk fibroin can be extracted from the cocoons of the B. mori silkworm and combined synergistically with other biomaterials to form biopolymer composites. With the development of recombinant DNA technology, silks can also be rationally designed and synthesized via genetic control. Silk proteins can be processed in aqueous environments into various material formats including films, sponges, electrospun mats and hydrogels. The versatility and sustainability of silk-based materials provides an impressive toolbox for tailoring materials to meet specific applications via eco-friendly approaches. Historically, silkworm silk has been used by the textile industry for thousands of years due to its excellent physical properties, such as lightweight, high mechanical strength, flexibility, and luster. Recently, due to these properties, along with its biocompatibility, biodegradability and non-immunogenicity, silkworm silk has become a candidate for biomedical utility. Further, the FDA has approved silk medical devices for sutures and as a support structure during reconstructive surgery. With increasing needs for implantable and degradable devices, silkworm silk has attracted interest for electronics, photonics for implantable yet degradable medical devices, along with a broader range of utility in different device applications. This Tutorial review summarizes and highlights recent advances in the use of silk-based materials in bio-nanotechnology, with a focus on the fabrication and functionalization methods for in vitro and in vivo applications in the field of tissue engineering, degradable devices and controlled release systems.

 

Methods Paper on Modeling of Protein-Based Biomaterials published in Extreme Mechanics Letter, April 2018

Extr. Mech. Lett., 2018, 20, 112-124

DOI: 10.1016/j.eml.2018.01.009

Scleroproteins are an important category of proteins within the human body that adopt filamentous, elongated conformations in contrast with typical globular proteins. These include keratin, collagen, and elastin, which often serve a common mechanical function in structural support of cells and tissues. Genetic mutations alter these proteins, disrupting their functions and causing diseases. Computational characterization of these mutations has proven to be extremely valuable in identifying the intricate structure–function relationships of scleroproteins from the molecular scale up, especially if combined with multiscale experimental analysis and the synthesis of model proteins to test specific structure–function relationships. In this work, we review numerous critical diseases that are related to keratin, collagen, and elastin, and through several case studies, we propose ways of extensively utilizing multiscale modeling, from atomistic to coarse-grained molecular dynamics simulations, to uncover the molecular origins for some of these diseases and to aid in the development of novel cures and therapies. As case studies, we examine the effects of the genetic disease Epidermolytic Hyperkeratosis (EHK) on the structure and aggregation of keratins 1 and 10; we propose models to understand the diseases of Osteogenesis Imperfecta (OI) and Alport syndrome (AS) that affect the mechanical and aggregation properties of collagen; and we develop atomistic molecular dynamics and elastic network models of elastin to determine the role of mutations in diseases such as Cutis Laxa and Supravalvular Aortic Stenosis on elastin’s structure and molecular conformational motions and implications for assembly.

 

Methods Paper on Modeling of Biomaterials published in Physica Scripta, April 2018

Phys. Scr., 2018, 93, 053003

DOI: 10.1088/1402-4896/aab4e2

In the 50 years that succeeded Richard Feynman's exposition of the idea that there is 'plenty of room at the bottom' for manipulating individual atoms for the synthesis and manufacturing processing of materials, the materials-by-design paradigm is being developed gradually through synergistic integration of experimental material synthesis and characterization with predictive computational modeling and optimization. This paper reviews how this paradigm creates the possibility to develop materials according to specific, rational designs from the molecular to the macroscopic scale. We discuss promising techniques in experimental small-scale material synthesis and large-scale fabrication methods to manipulate atomistic or macroscale structures, which can be designed by computational modeling. These include recombinant protein technology to produce peptides and proteins with tailored sequences encoded by recombinant DNA, self-assembly processes induced by conformational transition of proteins, additive manufacturing for designing complex structures, and qualitative and quantitative characterization of materials at different length scales. We describe important material characterization techniques using numerous methods of spectroscopy and microscopy. We detail numerous multi-scale computational modeling techniques that complements these experimental techniques: DFT at the atomistic scale; fully atomistic and coarse-grain molecular dynamics at the molecular to mesoscale; continuum modeling at the macroscale. Additionally, we present case studies that utilize experimental and computational approaches in an integrated manner to broaden our understanding of the properties of two-dimensional materials and materials based on silk and silk-elastin-like proteins.

 

IµBEAM Annual Meeting at MSM 2018 (IMAG Futures) Meeting, March 21-22, 2018

 

Method Paper on Multiscale Simulation and Protein Design published in ACS Biomaterials Science & Engineering, July 2017

ACS Biomater. Sci. Eng., 2017, 3 (8), pp 1542–1556

DOI: 10.1021/acsbiomaterials.7b00292

Silk is a promising material for biomedical applications, and much research is focused on how application-specific, mechanical properties of silk can be designed synthetically through proper amino acid sequences and processing parameters. This protocol describes an iterative process between research disciplines that combines simulation, genetic synthesis, and fiber analysis to better design silk fibers with specific mechanical properties. Computational methods are used to assess the protein polymer structure as it forms an interconnected fiber network through shearing and how this process affects fiber mechanical properties. Model outcomes are validated experimentally with the genetic design of protein polymers that match the simulation structures, fiber fabrication from these polymers, and mechanical testing of these fibers. Through iterative feedback between computation, genetic synthesis, and fiber mechanical testing, this protocol will enable a priori prediction capability of recombinant material mechanical properties via insights from the resulting molecular architecture of the fiber network based entirely on the initial protein monomer composition. This style of protocol may be applied to other fields where a research team seeks to design a biomaterial with biomedical application-specific properties. This protocol highlights when and how the three research groups (simulation, synthesis, and engineering) should be interacting to arrive at the most effective method for predictive design of their material.

Compressed files that includes the codes used for simulation could be found in the attachement of the paper:

http://pubs.acs.org/doi/suppl/10.1021/acsbiomaterials.7b00292 

MIT/IµBEAM Summer Course on Multiscale Materials Design, June 12-16, 2017

The course will focus on practical problem-solving computational tools paired with a detailed discussion of experimental techniques to probe the ultimate structure of materials, emphasizing tools to predict key mechanical properties. Case studies of molecular mechanics, bio-inspired composites, and dynamic fracture of composites and polymers will be presented and carried out by participants in computational labs. Simulation codes, algorithms, and details of the implementations of different simulation technologies, including validation, will be presented, including practical issues such as supercomputing (hardware and software), parallelization, Graphics Processing Computing (GPU), and others. A specific focus is on structural polymers and composites, including innovative material platforms such as carbon nanotubes, graphene, and protein materials. 

IµBEAM Annual Meeting at MSM 2017 (10^th Anniversary) Meeting, March 23-25, 2017

See our annual report slides here:

 

 

Fifth ASME Global Congress on Nanoengineering in Medicine and Biology (NEMB2016), February 21 - 24, 2016, Houston, TX, https://www.asme.org/events/nemb.aspx

The NEMB meeting included a series of sessions on modeling organized by IµBEAM that focused on multiscale thermal, optical, and mechanical modeling.  Plenay talks were given by John Bischof (Univ of Minnesota), Dennis Discher (University of Pennsylvania), Katherine Whittaker Ferrara (UC Davis), Kam Leong, (Columbia University), Nicholas Peppas (UT Austin), and Rebecca Richards-Kortum (Rice University)  

MSM IμBEAM Working Group – SITEP Updates , July 2016

The following topics will be presented at MMM 2016, 9-14 October (8th Multiscale Materials Modeling (MMM) international conference http://mmm2016.iop.org/home):

Wind Load Effect on Silkworm Silk Fiber Web Structure

Isabelle Su¹, Zhao Qin¹, Markus Buehler¹

¹Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

 

Abstract: Optimized by nature, silk exhibits remarkable mechanical strength, toughness and robustness to fulfill specific functions. Silk’s impressive properties originate from its hierarchical organization making it an inspiration for upscaling molecular properties to the macroscale. Silk is a protein which sequence dictates protein folding and consequently its macroscale mechanical properties. Silk’s stiffness arises from the crystalline region and its extensibility from the hidden length within the semi-amorphous region. As for cocoons, they have a complex three-dimensional multi-layered structure composed of a porous matrix reinforced of randomly oriented fibers. They are designed to withstand wind load. However, this study investigates how a single-layer silk architecture deflects and fails under wind load.

Here, experiments in the wind tunnel and simulations were carried out to investigate wind load effect on a cocoon silk web. The webs are spun by silkworms and subjected to an increasing wind load until failure. The models created are inspired inspired from microscopic scans and SEM of actual webs. Before failure, webs can deflect up to 11.4 mm at 38.9 m/s wind speed. Simulation results have shown the crucial role of fiber organization and web porosity in the robustness of the structure.

Understanding the mechanics across scales between fibers and the complex architecture of the web could contribute to material and structural optimization for bio-inspired composite material design. In particular, silk web-inspired designs could lead to high-performance, resilient and lightweight fiber-based materials.

 

Computational Smart Polymer Design based on Elastin Protein Mutability

Anna Tarakanova¹, Wenwen Huang², David L. Kaplan², Markus J. Buehler¹

¹Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

²Department of Biomedical Engineering, Tufts University, Medford, MA, USA

 

Abstract: Soluble elastin-like peptides (ELPs) can be engineered into a range of physical forms, from hydrogels and scaffolds to fibers and artificial tissues, finding numerous applications in medicine and engineering as “smart polymers”. Elastin-like peptides are attractive candidates as a platform for novel biomaterial design as they exhibit a highly tunable response spectrum, with reversible phase transition capabilities. Here, we report the design of a library of elastin-like protein material models, using Replica Exchange Molecular Dynamics (REMD) methods for enhanced sampling, to study the effect of sequence identity, chain length, and salt concentration on ELPs’ structural transition, exposing molecular mechanisms associated with such modifications. This library is a valuable resource for recombinant protein design and synthesis as it elucidates effects and mechanisms at the single-molecule level, paving a feedback path between simulation and experiment for smart material design.

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IµBEAM special journal issue: Multiscale Biomaterials: Integrated Experiment and Modeling, M.J. Buehler and G.M. Genin, eds.  Journal of the Royal Society, Interface Focus. 2016.

This special issue captures the state of the art of integrated multiscale biomaterials modeling and expeiment, and identifies key themes that arise across disciplines.  A dominant theme that arose from the work was is the challenge of uncovering and predicting hidden length and timescales, as described in our introductory article: http://rsfs.royalsocietypublishing.org/content/6/1/20150098

 

IµBEAM workshop on multiscale considerations for the study of tendon - March 5, 2016

Organizer: Stavros Thomopoulos, Columbia University

Venue: Annual meeting of the Orthopedic Research Society, Disneyworld

Abstract: Tendon is a hierarchical material with fibrillar structures from the molecular through tissue levels. At the nanoscale, collagen molecules pack together in a quarter-stagger array to form microfibrils. Neighboring microfibrils interdigitate, imposing order upon a mildly twisted lattice that forms the next level structure termed a fibril. At the next level of structural hierarchy, fibrils close-pack into larger structures to form fibers ~5 μm in diameter. The fibers then combine to form fascicles, which organize in the characteristic “crimp” pattern seen histologically. Finally, fascicles are bundled together through a fascicular membrane to form milli- to centi-meter scale tendon tissue. This highly ordered multiscale structure dictates the mechanical behavior of the tendon and the response of the resident cells. In order to better understand tendon behavior and pathology, careful consideration should be given to each hierarchical level and to the links between length scales. This workshop will describe the multiscale nature of tendon and the tools available for studying tendon at various length scales.

Program:

Introduction (Stavros Thomopoulos)

Multi scale tendon mechanics (Spencer Lake)

Cellular responses to tissue level deformation (Michael Lavagnino)

Tissue microstructural heterogeneity directs micromechanics and mechanobiology (Dawn Elliott)

Discussion panel (Stavros Thomopoulos, Dawn Elliott, Michael Lavagnino, Spencer Lake, and Jeffrey Weiss)

Strategic planning (Louis Soslowsky, Evan Flatow)

---

2015 IµBEAM Annual Meeting - September 8, 2015

• Venue: The IµBEAM committee held a meeting at the Tissue Engineering and Regenerative Medicine International Society annual meeting on Tuesday, September 8th from 11:45 am - 3:45 pm, in Salon B of the Boston Marriott, Copley Place.
• Outcomes: The theme that emerged from the meeting was a consensus that the design of advanced materials in engineering has always proceeded hand in hand with advances in our ability to understand mechanisms of deformation, resilience, and failure. The tools for modeling tissue-engineered systems have exploded in the past few years, and the integration of these tools with experiment is now maturing to the point that protein-to-tissue level modeling and associated material synthesis and characterization may soon become routine. The working group agreed to make a concerted effort to support the new ACS journal ACS Biomaterials Science and Engineering as a forum for publishing such work, and will organize a special issue on the topic.

IµBEAM on Intelligent design: multi-scale modeling of cells, tissues, and organs - September 8, 2015

• Orgainzers: Markus J. Buehler (MIT, mbuehler@MIT.EDU) and Guy Genin (WUSTL, genin@wustl.edu)
• Venue:  the Tissue Engineering and Regenerative Medicine International Society annual meeting on Tuesday, September 8th from 11:45 am - 3:45 pm, in Salon B of the Boston Marriott, Copley Place.
• Abstract: The workshop brought together leaders in the development and application of hierarchical modeling tools, experts in synthesis, processing and characterization, to discuss the state of the art and to identify challenges and opportunities.
• Program:

Session 1: Silk and silk-like materials modeling and experiment (SITEP). This session described fundamental methods and simple examples of how synthesis, processing and modeling are integrated in the case of silk and silk-like materials.

1.1 Fundamentals of modeling, Anna Tarakanova, MITThis talk covered the basics of molecular dynamics, multiscale modeling, with a case study/example.

1.2 Fundamentals of synthesis, Nina Dinjaski, Tufts UniversityThis talk described the basics of genetic engineering, batch processing, and practical techniques and their limitations.

1.3 Fundamentals of processing, Matthew Jacobson, Boston UniversityBasics of microfluidics – how microfluidic systems are made, modeling of flow, and applications in bioinspired silk fibers.

Session 2: Inspiring lunch keynote: The bone-tendon attachment, a resilient interface (Guy Genin, Washington University)

Abstract: All who have ever baked their own lunch have struggled with the challenge of preventing stiff burnt bits of food from peeling off of their lunch and sticking to the pan.  This challenge of adhesion between materials of dissimilar mechanical properties plagues designers across disciplines, from tissue engineering to civil engineering.  Nature presents a highly resilient solution at the interface between tendon and bone.  This session featured a guided discussion of engineering and physiological aspects of this fascinating interface, with examples from civil engineering to medicine to showcase the challenges.

Session 3: Tendon-to-bone modeling: This session described work on modeling and experiment of one of the most intriguing interfaces in nature, that of tendon and bone. The seccion focussed on mechanics of the nanoscale elements that comprise this interface, including cabonated hydroxylapatites, collagen, and osteopontin, and the latest tools being used to search for the roles of these elements in macroscale viscoelastic testing.

3.1 The role of carbonation in determining the size of hydroxylapatite particles, Guy Genin, Washington University

3.2 The role of carbonation in determining the fracture toughness of hydroxylapatite particles, Gang Seob Jung, MIT

3.3 The nanoscale foundation of viscoelasticity and energy absorption in partially mineralized tissues: first principles modeling of collagen and osteopontin,  Zhao Qin, MIT

3.4 Fast tools for viscoelastic spectral analysis of cells, collagen, and ECM remodeling, Guy Genin, Washington University

Session 4: Material world, the future: Perspectives. First principles design of materials for therapeutic applications is transforming tissue engineering. As the power of this toolbox is brought to bear, technologies that were once in the realm of science fiction are emerging as engineering realities.  In this final session, plenary talks by three leading experts discussed this exciting and shifting landscape, imagining what is possible and envisioning how this might shape our future.

4.1 Tailoring cell-material interfaces for drug delivery and tissue engineering applications, Joyce Wong, Boston UniversityThis talk presented new methods for cell-material interactions for a variety of applications.

4.2 The future of bioengineering materials in the materials genome world, David Kaplan, Tufts UniversityThis talk put the new capabilities into context for translational applications, tissue engineering, and medical aspects. 

4.3  Biomateriomics:  Bio-inspired composites, additive manufacturing, and printing models, Markus Buehler, MITThis talk presented work on 3D spider webs, scanning/modeling approaches, the translation into composites by design, and hierarchical materials with new properties.

 

2015 MSM Meeting: Satellite meeting of the IµBEAM working group

The timing of the 2015 IMAG meeting at Lister Hill coincided with that of the IµBEAM meeting in Boston.  A satellite meeting was held on September 8-9 at the IMAG meeting.  Dr. Brian Carlson from the University of Michigan School of Medicine served as chair.  The report from the meeting is contained in the following powerpoint file, presented by Dr. Carlson in at the general IMAG assembly held on the afternoon of September 9:

 

 Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C), Snowbird Utah, June 17-20, 2015 (http://sb3c.com)

• The conference is themed around the IµBEAM focus area of “Synergy of Modeling and Experiments in Biomechanics, Bioengineering and Biotransport.”  The program chair for this event is IµBEAM member Jeff Weiss (jeff.weiss@utah.edu).  All are invited to participate.
• Each track at the conference has sessions devoted to integration of theory and experiment in multiscale modeling.
• IµBEAM workshops:

1. 'The Constitutive Modeling and Parameter Estimation Challenge,” hosted by Victor Barocas and Vicky Nguyen.
2. "FeBIO, an open-access tool for multiscale modeling," hosted by Gerard Ateshian, Steve Maas, and Jeff Weiss
3. "CFD Challenge 2015,”  hosted by Kristian Valen-Sendstad and Kenichi Kono

IµBEAM International Coloquium Series: international webinar delivered by Markus Buehler, David Kaplan, and Joyce Wong - May 13, 2015

• Title: Predicting Biomaterials Structure-Function through Integrated Modeling-Experimental Approaches
• Presenters:  Markus Buehler (MIT), David Kaplan (Tufts), Joyce Wong (Boston Univ)

• Abstract: The speakers presented an update on their U01 project ("Models to predict protein biomaterial performance"). The webinar describes progress on establishing a set of tools, data, and software that will be shared with the community for multiscale simulation of processing, testing, and design of silk and silk-inspired fibers.  
• Material downloads: here (codes, instructions...). 

The ASME 2015 4th Global Congress on NanoEngineering for Medicine and Biology, April 19-22, 2015 in Minneapolis, MN

• The conference featured a track on multiscale modeling organized by WG members Victor Barocas and Sinan Keten.  All are invited to participate and to bring their trainees.
• An IMAG workshop was held onsite on April 19, organized by Markus Buehler, Guy Genin, and Grace Peng.  The focus of the workshop was multiscale modeling of fibrous tissues. Sinan Keten, Michael Sacks, and Vivek Shenoy presented.  
• Link: http://www.asmeconferences.org/NEMB2015/

IµBEAM International Colloquium Serires: international webinary delivered by Sinan Keten - February 4, 2015

• Tuning the entropic spring to dictate order and functionality in polymer conjugated peptide biomaterials

IµBEAM International Colloquium Series: international webinar delivered by Robert Latour - November 24, 2014

• Presenter: Robert Latour (Clemson)
• Title: Multiscale Modeling to Predict the Structure and Bioactivity of Adsorbed Proteins on Biomaterials Surfaces

IµBEAM International Colloquium Series: international webinar delivered by Vivek Shenoy - October 15, 2014

• Presenter: Vivek Shenoy (Penn)
• Title: Cell-Matrix interactions in 3D microtissues: Multiscale mechanical models.

2014 IMAG Meeting, NIH Campus, September 3, 2014

• David Kaplan, Joyce Wong, Markus Buehler are scheduled to give a special presentation at the 2014 MSM Meeting.
• The ImuBEAM will have a '''breakout session at the IMAG 2014 meeting''' (September 3, 2014; 12:45 – 2:15pm; Bldg. 45 Balcony B).

Agenda: WG participants and interested attendees will discuss activities, challenges and new opportunities. The WG leadership will report back to the IMAG community in a plenary presentation at 5:10-5:20 pm.

•  For the agenda, and other information please see: http://www.imagwiki.nibib.nih.gov/mediawiki/index.php?title=2014_MSM_CON...

2014 WCB, Boston, MA, June, 2014

• The World Congress on Biomechanics (http://wcb2014.com) included three symposia and one workshop on integrated multiscale experiment and modeling, organized by our working group.  The first was a series of sessions co-organized by Stavros Thomopoulos on the multiscale mechanics of hierarchical tissues.  Markus Buehler co-organized a session on design, fabrication, and analysis of hierarchical tissues.  Guy Genin and Roland Kaunas organized a series of sessions on integration of theory and experiment in multi-scale modeling of living cells; Viola Vogel presented a keynote talk in this symposium.  Guy Genin also co-organized an NSF-sponsored workshop on the role of multiscale modeling in the BRAIN initiative.  Jeff Weiss presented a multiple-session symposium on multiscale modeling using the FEBio platform.

SITEP Workshop, Tufts University, June 10, 2014

• Purpose: The purpose of the retreat was to have in-depth discussions of all project parts, challenge students and postdocs from all three research groups to jointly prepare and present materials, and to collectively discuss next steps and plans for the next year.  Collection of slides from the retreat can be downloaded [http://www.imagwiki.nibib.nih.gov/mediawiki/images/f/f6/IMAG_U01_retreat... here].
• Agenda: http://www.imagwiki.nibib.nih.gov/mediawiki/images/2/22/SITEP-retreat_U0...
• Participants: All team members of the U01 grant, and several visitors, including Professor Carole Perry (University of Nottingham, UK)
• Download images: [http://www.imagwiki.nibib.nih.gov/mediawiki/images/5/55/SITEP_retreat_-2... Audience] [http://www.imagwiki.nibib.nih.gov/mediawiki/images/1/15/SITEP-retreat_20... Presenters].

IµBEAM International Colloquium Series: international webinar delivered by Jeff Holmes - May 21, 2014

• Title: Multi-Scale Modeling of Scar Formation: Towards In Situ Design of Better Scar
• Presenter: Jeff Holmes (Virginia)
• Archived presentation: https://www.youtube.com/watch?v=883ZoUpyaAM

IµBEAM International Colloquium Series: international webinar delivered by Markus Buehler, Guy Genin, and Stavros Thomopoulos, February 10, 2014

• Title: Challenges in integrating experiment and models across scales at the attachment of tendon to bone
• Presenters: Markus Buehler (MIT), Guy Genin (Washington Univ), and Stavros Thomopoulos (Columbia)
• Partial set of slides: http://www.imagwiki.nibib.nih.gov/mediawiki/images/7/7f/NIH_WG_slides_Fe...

NEMB 2014, San Francisco, CA, Feb. 2-5, 2014

• The ASME 2014 3rd Global Congress on NanoEngineering for Medicine and Biology (NEMB2014) was held Feb. 2-5, 2014 in San Francisco, CA (http://www.asmeconferences.org/nemb2014/). The 2014 Congress focused on the integration of engineering, materials science, and nanotechnology in addressing fundamental problems in biology and medicine, and had a h4 focus on integration of experiment and modeling for biomaterials. Plenary and keynote speakers relevant to our working group included Paul Alivisatos, Mina Bissell, Tejal Desai, Albert Folch, Dorit Hanein, Kam Leong, Luke Lee, CT Lim, Arun Majumdar, Kit Parker, Stephen Quake, G. Ravichandran, John Rogers, Molly Stevens, Sam Stupp, Mehmet Toner, and Jennifer West.  IμBEAM members played central roles on the organizing committee: Markus Buehler was honorary chair of the conference, Guy Genin served on the steering committee, and Roland Kaunas, Paolo Provenzano, and Feng Xu served as track chairs.

NEMB 2013, Boston, MA, February, 2013

• This conference was a great success. Held in February 2013 in Boston, it featured top plenary lectures by acclaimed scientists such as Robert Langer, Rakesh Jain, David Mooney, Sam Gambhir and Don Ingber (http://www.asmeconferences.org/NEMB2013/). The conference included many stimulating discussions on multiscale experiment and modeling.  The Conference Chair, Markus Buehler, and the Program Chair, Guy Genin now co-lead the IμBEAM Working Group. Other outcomes of the conference included scientific discussions, several tutorials for young scientists.  The conference was an excellent forum overall for the integration of medical and engineering sciences.   The NEMB conference was incredibly successful and a follow-up conference was held in 2014.

2013 IMAG Meeting, NIH Campus

• "Integrated Computational Modeling and Experimental Design of Functional Protein Biomaterials" by Shangchao Lin, Olena Tokareva, Anna Tarakanova, Matthew Jacobsen, Wenwen Huang, Qin Wang, David Li, Joyce Y. Wong, David L. Kaplan, and Markus J. Buehler (NIH U01 EB014976): http://www.imagwiki.nibib.nih.gov/mediawiki/images/2/23/IMAG_MSM_Poster_... Poster download (PDF)