Materials by design: modeling and manufacturing


Research at LAMM

Our lab's research 

Our research focus on the development of a new paradigm to enable the design, synthesis and manufacturing of materials and structures from the molecular scale. This requires the combination of multi-scale modeling, additive manufacturing, 3D printing, and experimental synthesis, which is then applied to bio-inspired materials, biological materials, nanomaterials, and biomass materials, just to mention a few. By utilizing a computational materials science approach that includes Density functional theory (DFT) calculations, Molecular Dynamics (MD) simulations, coarse-grained and finite element modeling we aim to understand and design materials along all different length scales, from a fundamental level. This is combined with additive manufacturing and synthesis techniques to provide a complete framework for materials design and production. By incorporating concepts from structural engineering, materials science and biology our lab's research has identified the core principles that link the fundamental atomistic-scale chemical structures to functional scales by understanding how biological materials achieve superior mechanical properties through the formation of hierarchical structures, via a merger of the concepts of structure and material.



One of our goals is to understand the mechanics of deformation and failure of biology's construction materials at a fundamental level. The deformation and failure of engineering materials has been studied extensively, and the results have impacted our world by enabling the design of advanced materials, structures and devices. However, the mechanisms of materials failure in biological systems are not well understood and thus present an opportunity to institute a new paradigm of materials science at the interface of engineering and biology. 

Proteins are a major application area in our lab, and serve as a model material to understand complex hierarchical manufacturing and material processes. Proteins are the main building blocks of life—universally composed of merely about 20 distinct amino acids—realize a diversity of material properties that provide structural support, locomotion, energy and material transport, to ultimately yield multifunctional and mutable materials. Despite this functional complexity, the makeup of biological materials is often simple and has developed under extreme evolutionary pressures to facilitate a species' survival in adverse environments. As a result, materials in biology are efficiently created with low energy consumption, under simple processing conditions, and are exquisite as they often form from a few distinct, however abundantly available, repeating material constituents. 

Interestingly, these abundant material constituents (such as H-bonds) are often functionally inferior and extremely weak. Yet, materials such as silk, collagen in tendon and bone, or intermediate filament proteins that make up cells and hair are highly functional, mutable, and some even stronger than steel. It is therefore an elementary question how Nature can achieve such functional material properties in spite of severe environmental constraints.







Cover article in Integrative Biology, focused on nanomechanical sequencing of collagen nanofibrils.

This work involved a systematic analysis of how mechanical properties depend on the amino acid sequence of the collagen molecule.

(link to paper...)










Spiders spin intricate webs that serve as sophisticated prey-trapping architectures that simultaneously exhibit high strength, elasticity and graceful failure. To determine how web mechanics are controlled by their topological design and material distribution, here we create spider-web mimics composed of elastomeric filaments. Specifically, computational modelling and microscale 3D printing are combined to investigate the mechanical response of elastomeric webs under multiple loading conditions. We find the existence of an asymptotic prey size that leads to a saturated web strength. We identify pathways to design elastomeric material structures with maximum strength, low density and adaptability. We show that the loading type dictates the optimal material distribution, that is, a homogeneous distribution is better for localized loading, while stronger radial threads with weaker spiral threads is better for distributed loading. Our observations reveal that the material distribution within spider webs is dictated by the loading condition, shedding light on their observed architectural variations (Nature Communications, DOI: 10.1038/ncomms8038).



We combine in situ transmission electron microscopy and large-scale molecular dynamics simulations to investigate brittle fracture in 2D monolayer MoS2, revealing that cracks propagate with a tip of atomic sharpness through the preferential direction with least energy release. We find that sparse vacancy defects cause crack deflections, while increasing defect density shifts the fracture mechanism from brittle to ductile by the migration of vacancies in the strain fields into networks. The fracture toughness of defective MoS2 is found to exceed that of graphene due to interactions between the atomically sharp crack tips and vacancy clusters during propagation. These results show that monolayer 2D materials are ideal for revealing fundamental aspects of fracture mechanics not previously possible with thicker materials, similar to studies of dislocation behavior in 2D materials.

Figure reprinted from ACS Nano, 2016 (link to paper...)


Main findings and impact

By incorporating concepts from structural engineering, materials science and biology our lab's research has identified the core principles that link the fundamental atomistic-scale chemical structures to functional scales by understanding how biological materials achieve superior mechanical properties through the formation of hierarchical structures, via a merger of the concepts of structure and material. Our work has demonstrated that the chemical composition of biology's construction materials plays a minor role in achieving functional properties. Rather, the way components are connected at distinct scales defines what material properties can be achieved, how they can be altered to meet functional requirements, and how they fail in disease states. 

Similar to conventional engineering testing of materials (e.g. by exposing them to severe stress to break them) our research approach is based on using the study of materials failure as a tool to elucidate the design principles of how functional material properties are achieved, and how they are lost. We apply an experimentally validated multi-scale modeling and simulation approach that considers the structure-process-property paradigm of materials science and the architecture of proteins at multiple levels, from the atomistic (chemistry, molecular) scale up to the overall structural scale (material, tissue, spider web). My research has resulted in an engineering paradigm that facilitates the analysis and design of sustainable materials, starting from the molecular level, which mimic and exceed the properties of biological ones while being constructed from abundant and intrinsically poor material constituents. 

Civil engineering is a broad subfield of engineering that focuses on strategies to develop and maintain the infrastructures to enable and evolve modern civilization. Environmental engineering is concerned with the complex interaction of synthetic structures with natural environments, and with development of environmentally friendly engineering concepts. In both fields, materials and their properties play an essential role for many applications. Its fundamental, theoretical and scientific understanding is the primary goal of the research carried out in our lab. For example, a better understanding of the failure mechanisms of materials has high impact in preventing failure of existing structures. The development of new materials may lead to better designs and could replace classical designs, as for example by using enviromentally friendly coatings, functional surfaces or new construction materials.



The Mytilidae, generally known as marine mussels, are known to attach to most substrates including stone, wood, concrete and iron by using a network of byssus threads. Mussels are subjected to severe mechanical impacts caused by waves. However, how the network of byssus threads keeps the mussel attached in this challenging mechanical environment is puzzling, as the dynamical forces far exceed the measured strength of byssus threads and their attachment to the environment. Here we combine experiment and simulation, and show that the heterogeneous material distribution in byssus threads has a critical role in decreasing the effect of impact loading.We find that a combination of stiff and soft materials at an 80:20 ratio enables mussels to rapidly and effectively dissipate impact energy. Notably, this facilitates a significantly enhanced strength under dynamical loading over 900% that of the strength under static loading (Nature Communications, DOI: 10.1038/ncomms3187).


Merger of structure and material 

Biological protein materials provide the foundation for the integration of structure and material, thereby enabling the inclusion of molecular and multi-scale features in the material design process to realize a unique combination of properties despite the intrinsic weakness and simplicity of constituents.

We are in particular interested in the combination of disparate properties in biological materials, such as strength, robustness, deformability, adaptability, changeability, and evolvability as well as mutability. Our lab uses principles developed in civil engineering and architecture applied at all scales including the nanoscale in the analysis and design of materials.


Multiscale materials science of biological materials and structures: Materiomics 

The properties of biological materials have been the focal point of extensive studies over the past decades, leading to formation of an active research field that intimately connects biology, chemistry and materials science.  Significant advances have been made throughout many disciplines and research areas, ranging throughout a variety of material scales, from atomistic, molecular up to continuum scales. Experimental studies are now carried out with molecular precision, including investigations of how molecular defects such as protein mutations or protein knockout influence larger length- and time-scales.  Simulation studies of biological materials now range from electronic structure calculations of DNA, molecular simulations of proteins and biomolecules like actin and tubulin to continuum theories of bone and collagenous tissues.  The integration of predictive numerical studies with experimental methods represents a new frontier in materials research.  This field is now at a turning point where major breakthroughs in the understanding, synthesis, control and analysis of complex biological systems emerge.

These advances have resulted in the formation of a new research field referred to as materiomics. Materiomics is defined as the study of the material properties of natural and synthetic materials by examining fundamental links between processes, structures and properties at multiple scales, from nano to macro, by using systematic experimental, theoretical or computational methods. This term has been coined in analogy to genomics, the study of an organism's entire genome. Similarly, materiomics refers to the study of processes, structures and properties of materials from a fundamental, systematic perspective by incorporating all relevant scales, from nano to macro, in the synthesis and function of materials and structures. The integrated view of these interactions at all scales is referred to as a material's materiome. The broader field of materiomics encompasses the study of a broad range of materials, which includes biological materials and tissues, metals, ceramics and polymers. Among others, materiomics finds applications in elucidating the biological role of materials in biology, for instance in the progression and diagnosis or the treatment of diseases. It also includes the transfer of biological material principles in biomimetic and bioinspired applications, and the study of interfaces between living and non-living systems. 

A particular focus in our lab is the application of materiomics to the study of failure behavior in the biological context of materials through a computational materials science approach. By learning from how materials break down, we identify the fundamental makeup of materials, and how materials can be improved to provide critical functions, robustly. 

Link to article on Materiomics....


Research highlights 

The basis to our work are three major types of protein material building blocks that define the structural basis of ubiquitous biological materials. Starting from the chemical composition of three distinct classes of protein materials allows a dual purpose; to elucidate how they provide a diversity of functions despite being constructed from the same universal building blocks and to enable rigorous comparative analyses where a simple, identical model can be used systematically for various major protein material classes. The protein materials investigated in our laboratory are: 

•   Collagenous materials and tissues (predominant in materials under strain or compression; tendon, skin, bone and teeth)

•   Beta-sheet rich materials (primary component in spider silk and silkworm silk, muscle tissue and amyloid protein)

•   Alpha-helix rich materials (key constituent of protein intermediate filaments structures in cells and materials such as hoof, hair and wool).

Currently most molecular deformation and failure mechanisms and properties of protein materials (from the atomistic level up to the micrometer length- and microsecond time-scales) remain inconclusively defined. Our multi-scale modeling approach has successfully overcome the challenge of linking atomistic models to mesoscale material properties, and has resulted in defining the governing mechanisms associated with protein material mechanics. In the following sections we describe first the methods and the review examples of the three main application areas. 


Multi-scale modeling and simulation of biological and bioinspired materials and structures



We develop and apply new simulation techniques based on multi-scale simularion and analysis, used to capture materials phenomena at the intermediate, mesoscopic scale. This enables the integration of computational and theoretical methods with experimental analysis and characterization methods (see, e.g. Buehler and Yung, Nature Materials, 2009; link to paper...).



The approach to develop systematic relations between structures, processes and properties across the scales is the key impact of materiomics. 

The figure on the left depicts this hierarchical materials science paradigm applied to biological materials and tissues. The variables Hi refer to hierarchy levels =0.. N, and Ri refer to material property requirements at hierarchy levels =0.. N. 

This method sheds light on fundamental question of universality and diversity of the structural makeup of protein materials, revealing fundamental evolutionary principles that control their structures and how functions are enabled.



This multiscale approach finds numerous applications in the analysis of key natural and synthetic materials as illustrated below.



Webmasters' secrets

Spiders and silkworms are masters of materials science, but scientists are finally catching up. Silks are among the toughest materials known, stronger and less brittle, pound for pound, than steel. Our work has unraveled some of their deepest secrets that could lead the way to the creation of synthetic materials that duplicate, or even exceed, the extraordinary properties of natural silk. 

Link to MIT News Article...

Link to Nature Materials paper...


This multiscale approach finds numerous applications in the analysis of key natural and synthetic materials as illustrated below.



Selected publications

M.J. Buehler, “Tu(r)ning weakness to strength,” Nano Today, Vol. 5 , pp. 379-383, 2010 (link to paper...MIT News Article “Going nature one better")

S. Cranford, M.J. Buehler, “Materiomics: Biological Protein Materials, from Nano to Macro”, Nanotechnology, Science and Application, Vol. 3, pp. 127-148, 2010 (link to paper...). 

D. Sen, M.J. Buehler, “Size and geometry effects on flow stress in bioinspired de novo metal-matrix nanocomposites”, Advanced Engineering Materials, Vol. 11(10), pp. 774-781, 2009 (link to paper...

M.J. Buehler, Y. Yung, “Deformation and failure of protein materials in extreme conditions and disease”, Nature Materials, Vol. 8(3), pp. 175-188, 2009 (link to paper...

S. Cranford, D. Sen, M.J. Buehler, “Meso-Origami: Folding Multilayer Graphene Sheets”, Applied Physics Letters, Vol. 95, paper #: 123121, 2009 (link to paper...)

J. Bertaud, Z. Qin, M.J. Buehler, “Amino acid sequence dependence of nanoscale deformation mechanisms in alpha-helical protein filaments”, Journal of Strain Analysis, Vol. 44(7), pp. 517-531, 2009 (link to paper...).

J. Bertaud, Z. Qin, M.J. Buehler, “Atomistically informed mesoscale model of alpha-helical protein domains”,International Journal for Multiscale Computational Engineering, Vol. 7(3), pp. 237-250, 2009 (lik to paper...

S. Cranford, M.J. Buehler, “Mechanomutable Carbon Nanotube Arrays”, International Journal of Material and Structural Integrity, Vol. 3(2-3),  pp. 161-178, 2009 (link to paper...

T. Ackbarow, D. Sen, C. Thaulow, M.J. Buehler, “Alpha-Helical Protein Networks are Self Protective and Flaw Tolerant”, PLoS ONE, Vol. 4(6), paper # e6015, 2009 (link to paper...

M.J. Buehler, Y. Yung, “Deformation and failure of protein materials in extreme conditions and disease”, Nature Materials, Vol. 8(3), pp. 175-188, 2009 (link to paper...

M.J. Buehler and T. Ackbarow, “Nanomechanical strength properties of hierarchical biological materials and tissues”, Computer Methods in Biomechanics and Biomedical Engineering, Vol. 11(6), pp. 595-607, 2008 (link to paper...

D. Sen and M.J. Buehler, “Simulating chemistry in mechanical deformation of metals,” International Journal for Multiscale Computational Engineering, Vol. 5(3-4), pp. 181-202, 2007


Collagenous materials and tissues: Structure, deformation and failure 

Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to organisms and is thus the prime construction material in biology. Collagen is also the dominating material in the extracellular matrix where its stiffness controls cell differentiation, growth and pathology. We apply atomistic based hierarchical multiscale modeling to describe this complex biological material from the bottom up. Our hierarchical multi-scale simulation scheme enables us to develop a fundamental, atomistic based description of collagenous materials.



Our molecular model of collagen is used to investigate several aspects related to collagen based tissues, including source of elasticity, fracture behavior, molecular origin of diseases, synthesis of synthetic collagen and the mechanics of mineralized tissue such as bone .Current activities focus on disease related aspects, for example in osteogenesis imperfecta (brittle bone disease) as well as Alport syndrome. We are also interested in using collagen as a building block for de novo peptide and protein materials. 

In a series of publications we developed a multi-scale model of collagen that enabled us to predict the elastic, plastic and failure mechanisms and properties at different material scales, from single molecules (polypeptides) to collagen fibrils (micrometer length-scale) and the continuum tissue scale, with the ability to explicitly consider variations in the (genetically defined) amino acid sequence of the molecular building blocks.






Until now, collagen materials have primarily been described at macroscopic scales, without explicitly understanding the mechanical contributions at the molecular and fibrillar levels. Our understanding at this level is critical to the development of fundamental models of collagenous tissues, important to the design of new scaffolding biomaterials for regenerative medicine. We have validated key predictions of our model through quantitative comparison with experimental results (with optical tweezers and AFM), specifically elasticity and rupture strength. 

For the case of collagen materials, we showed that the mechanical strength reaches a plateau at molecular lengths beyond 200 nm. The discovery of this size effect is important as it provides an explanation for the highly conserved and universal occurrence of molecular lengths in collagen tissues that range from 200-400 nm. Evidence for the breakdown of this material design concept can be found under diseased states of collagen (specifically in brittle bone disease), where the formation of stress concentrations leads to heterogeneous stress and results in the reduced strength and toughness of the tissue. 


Selected publications

A. Russo, A. Gautieri, S. Vesentini, A. Redaelli, M.J. Buehler, "Coarse-grained model of collagen molecules using an extended MARTINI force field”, Journal of Chemical Theory and Computation , Vol. 6(4), pp. 1210-1218, 2010.

A. Gautieri, S. Uzel, S. Vesentini, A. Redaelli, M.J. Buehler, “Molecular and mesoscale disease mechanisms of Osteogenesis Imperfecta”, Biophysical J., Vol. 97(3), pp. 857-865, 2009 (link to paper...

M. Srinivasan, S.G.M. Uzel, A. Gautieri, S. Keten, M.J. Buehler, “Alport Syndrome mutations in type IV tropocollagen alter molecular structure and nanomechanical properties” Journal of Structural Biology, Vol.168(3), pp. 503-510, 2009 (link to paper...). 

H. Tang, M.J. BuehlerB. Moran, “A Constitutive Model of Soft Tissue: From Nanoscale Collagen to Tissue Continuum”, Annals of Biomedical Engineering,Vol. 37(6), pp. 1117-1130, 2009 (link to paper...

S. Uzel, M.J. Buehler, “Nanomechanical sequencing of tropocollagen molecules”, Integrative Biology, Vol 1(7), pp. 452-459, 2009 (link to paper...

A. Gautieri, S. Vesentini, A. Redaelli, M.J. Buehler, “Single molecule effects of osteogenesis imperfecta mutations in tropocollagen protein domains”, Protein Science, Vol. 18(1), pp. 161-168, 2009 (link to paper...)

M.J. Buehler, “Nanomechanics of collagen fibrils under varying cross-link densities: Atomistic and continuum studies”, Journal of the Mechanical Behavior of Biomedical Materials, Vol. 1, pp. 59-67, 2008 ( link to paper...)

M.J. Buehler and S.Y. Wong, " Entropic elasticity controls nanomechanics of single tropocollagen molecules", Biophys. J. Vol. 93(1), pp. 37-43, 2007 (link to paper).

M.J. Buehler, "Nature designs tough collagen: Explaining the nanostructure of collagen fibrils", Proc . Nat'l Academy of Sciences USA, Vol. 103 (33), pp. 12285–12290, 2006 (link to paper...)


Plasticity and fracture mechanics of bone 

Based on our modeling of pure collagenous materials we also develop fundamental bottom-up models of the mechanics of mineralized collagenous tissues, and in particular bone. A key difference to pure collagenous tissues such as tendon is the existence of a mineral phase, where small hydroxyapatite (HA) crystals form in the gap regions of collagen fibrils.



In the figure shown here molecular modeling is used to study the elementary deformation mechanisms of fracture of bone materials. This provides insight into the origin of bone's great toughness, relative high strength and light weight. 

Further reading: 

Molecular nanomechanics of bone: 

fibrillar toughening by mineralization (link to Nanotechnology paper ... )

MIT probes secret of bone's strength (link to MIT News article...)





Selected publications

M.E. Launey, M.J. Buehler, R.O. Ritchie, “On the mechanistic origins of toughness in bone,” Annual Review of Materials Science, Vol. 40, pp. 4175-4188, 2010.

M.J. Buehler, S. Keten, “Failure of molecules, bones, and the earth itself”, Rev. Mod. Phys., Vol. 82(2), 2010 (link to paper...); associated article: M. Buchanan, “Learning from Failure”, Nature Physics , Vol. 5, pp. 705, 2009 (link to paper...

R. Ritchie, M.J. Buehler, P. Hansma, “Plasticity and toughness in bone”, Physics Today, Vol. 62(6), pp. 41-47, 2009; cover article (link to paper...

H.D. Espinosa, J.E. Rim, F. Barthelat, M.J. Buehler, “Merger of Structure and Material in Nacre and Bone - Perspectives on de novo Biomimetic Materials”, Progress in Materials Science, Vol. 54, pp. 1059-1100, 2009 (link to paper...

M.J. Buehler, "Defining nascent bone by the molecular nanomechanics of mineralized collagen fibrils", Nanotechnology, Vol. 18, paper number 295102, 2007 (link to paper...)


Beta-sheet rich protein materials: Silks and amyloid proteins 

Structure and mechanical properties of spider silk 

The ultrastructure of protein materials such as spider silk, muscle tissue or amyloid fibers consists primarily of beta-sheets structures, composed of hierarchical assemblies of H-bonds.  Despite the weakness of H-bond interactions – intermolecular bonds 100 to 1,000 times weaker than those in ceramics or metals –  these materials combine exceptional strength, robustness and resilience.  We discovered that the rupture strength of H-bond assemblies is governed by geometric confinement effects, suggesting that clusters of at most 3-4 H-bonds break concurrently, even under uniform shear loading of a much larger number of H-bonds. This universally valid result leads to an intrinsic strength limitation that suggests that shorter strands with less H-bonds achieve the highest shear strength.  Our finding explains how the intrinsic strength limitation of H-bonds is overcome by the formation of a nanocomposite structure of H-bond clusters, enabling the formation larger, much stronger beta-sheet structures. Our results explain recent proteomics data, suggesting a correlation between shear strength and prevalence of beta-strand lengths in biology. 

In another study, we discovered universal scaling laws that characterize the size-dependent strength properties of H-bond clusters found in beta-sheet protein structures (e.g. beta-sheet nanocrystals that form cross-linking domains in silk) revealed that beta-sheet nanocrystals confined to less than 2-3 nanometers achieve a much higher stiffness, strength and mechanical toughness than larger nanocrystals. We discovered the reason behind this phenomenon is that confinement ensures uniform shear deformation that makes most efficient use of H-bonds, whereas the emergence of dissipative molecular stick-slip deformation due to the weak nature of H-bonds lead to significantly enhanced toughness. Our findings provide an explanation for recent experimental studies that have demonstrated that even a slight increase in the beta-sheet nanocrystal size results in a severe drop in the overall strength and toughness of spider silk, and confirms our theoretical prediction that size effects are crucial to explaining how the weakness of H-bonds is overcome. 

More generally, these findings provide a quantitative explanation for geometrically confined hierarchical structures in protein materials. Our work demonstrated that this universal design principle is indeed found broadly throughout biology and is realized in a diverse range of materials including silk, muscle proteins and others, serving as a powerful paradigm of the mechanisms that enable biological systems to turn weakness into strength.



H-bond networks in protein materials such as spider silk, forming biology's universal cement (S. Keten and M.J. Buehler, Nano Letters, 2008; link to paper...; S. Keten et al., Nature Materials, 2010; link to paper...).


Selected publications

S. Keten, M.J. Buehler, “Nanostructure and molecular mechanics of dragline spider silk protein assemblies”, Journal of the Royal Society Interface, accepted for publication (link to paper...), paper highlighted in Science (link to article...)

A. Nova, S, Keten, N. Pugno A. Redaelli , M.J. Buehler , “Molecular and nanostructural mechanisms of deformation, strength and toughness of spider silk fibrils”, Nano Letters , Vol. 10(7), pp. 2626-2634, 2010 (link to paper...)

F. Bosia, N.M. Pugno, M.J. Buehler, “Hierarchical simulations for the design of supertough nanofibers inspired by spider silk,” Physical Review E, Vol. 82, paper # 056103, 2010. 

S. Keten, M.J. Buehler, “Atomistic model of the spider silk nanostructure”, Applied Physics Letters , Vol. 96, paper # 153701, 2010. Cover article. 

S. Keten, Z. Xu, B. Ihle, M.J. Buehler, “Nanoconfinement controls stiffness, strength and mechanical toughness of beta-sheet crystals in silk”, Nature Materials , Vol. 9, pp. 359-367, 2010 (link to paper...

T. Ackbarow, S. Keten, and M.J. Buehler, "A multi-timescale strength model of alpha-helical protein domains", J. Phys.: Condens. Matter, Vol. 21, paper # 035111, 2009 

S. Keten and M.J. Buehler, "Asymptotic strength limit of hydrogen bond assemblies in proteins at vanishing pulling rates", Physical Review Letters Vol. 100, paper number 198301 (link to paper...)

S. Keten and M.J. Buehler, “Geometric Confinement Governs the Rupture Strength of H-bond Assemblies at a Critical Length Scale”, Nano Letters, Vol. 8(2), 2008 (link to paper...

S. Keten and M.J. Buehler,  “The strength limit of entropic elasticity in beta-sheet  protein domains”, Physical Review E, Vol. 78(6), paper number 061913, 2008

T. Ackbarow, X. Cheng, S. Keten and M.J. Buehler, "Hierarchies, multiple energy barriers and robustness govern the fracture mechanics of alpha-helical and beta-sheet protein domains ", Proc . Nat'l Academy of Sciences USA, Vol. 104(42), pp. 16410-16415, 2007 (cover article, link to paper...EurekAlert! press release...CEE News Item...).

Amyloid fibrils and other beta-sheet rich materials 

Amyloids are highly organized protein filaments, rich in beta-sheet secondary structures, that self-assemble to form dense plaques in brain tissues affected by severe neurodegenerative disorders (e.g. Alzheimer’s Disease). Identified as natural functional materials in bacteria, in addition to their remarkable mechanical properties, amyloids have also been proposed as a platform for novel biomaterials in nanotechnology applications including nanowires, liquid crystals, scaffolds and thin films. Our work focuses on developing structural models of amyloid fibrils and the analysis of physical material properties of fibrils, fibers, and amyloid plaques. We use a series of computational tools to achieve this. In addition to work focused on amyloids, we also emphasize on studies of beta-solenoids, protein nanotubes, and other fibrous beta-sheet materials.


The image above depicts the hierarchical structure of amyloid protein material, from atoms to plaques or biofilms. Our work focuses on explaining mechanical properties at distinct hierarchical levels by using a multiscale modeling approach that links nano to macro. 


Selected publications

R. Paparcone, S. Cranford, M.J. Buehler, “Self-folding and aggregation of amyloid nanofibrils,” in submission 

R. Paparcone, M.J. Buehler, “Failure of A-beta-(1-40) amyloid fibrils under tensile loading,” Biomaterials, accepted for publication (link to article....

R. Paparcone, M. Pires, M.J. Buehler, “Mutations alter geometry and mechanical properties of Alzheimer's Aß(1-40) amyloid fibrils,” Biochemistry 49 , 8967–8977, 2010. 

R. Paparcone, S. Keten, M.J. Buehler, “Nanomechanical properties of Alzheimer's Aß(1-40) amyloid fibrils under compressive loading”, J. Biomechanics , Vol. 43(6), pp. 1196-1201, 2010 (link to paper...

Z. Xu, R. Paparcone, M.J. Buehler, “Alzheimer's Aß(1-40) amyloid fibrils feature size dependent mechanical properties”, Biophysical Journal , Vol. 98(10), pp. 2053-2062, 2010 (link to paper...

R. Paparcone, M.J. Buehler, “Failure of Alzheimer's Aß(1-40) amyloid nanofibrils under compressive loading”, JOM , Vol. 62(4), pp. 64-68, 2010. 

R. Paparcone, M.J. Buehler, “Microscale structural model of Alzheimer’s A-beta(1-40) amyloid fibril”, Applied Physics Letters, Vol. 94, paper # 243904, 2009 (link to paper...)

S. Keten, J.F. Alvarado, S. Muftu, M.J. Buehler, “Nanomechanical characterization of the triple beta-helix domain in the cell puncture needle of bacteriophage T4 virus”, Cellular and Molecular Bioengineering, Vol. 2(1), pp. 66-74, 2009 (link to paper...

S. Keten and M.J. Buehler, “Large deformation and fracture mechanics of a beta-helical protein nanotube: Atomistic and continuum modeling", Computer Methods in Applied Mechanics and Engineering, Vol. 197(41-42), pp. 3203-3214, 2008 (link to paper...)

Alpha-helix rich intermediate filament protein materials, from nano to macro 

In metazoan cells, actin microfilaments and microtubules found in the cytoskeleton are accompanied by a third filament system, intermediate filaments. These fibrous proteins are absent from both plants and fungi, and have been linked to serious human diseases including cancer, muscle dystrophies and the rapid aging disease. Their name, “intermediate filaments,” was coined back in the 1970s because their diameter of about 10 nm appeared to be intermediate in size between those of myosin thick filaments and actin microfilaments. More recently, the interest in intermediate filaments has increased substantially as it became clear that they are critical to many important cellular functions. 

Although intermediate filaments have been discovered more than 30 years ago, their molecular level structure and nanomechanical properties remain elusive. Notably, being an extremely stretchy filament (that can be stretched to four times its initial length) – and thereby distinguishing itself noticeably from the other cytoskeletal proteins – the mechanical properties of intermediate filaments play a major role in biology. In fact, researchers termed intermediate filaments the “safety belt of cells” to describe their ability to give strength and support to cells and the nuclear envelope at very large deformation. Indeed, cells without or with much fewer intermediate filaments loose their stretchiness, leading to severe diseases. However, the source of the extreme stretchiness of this protein remains elusive, partly due our lack of an ability to directly image the molecular structures and mechanisms that define the properties of intermediate filaments.



The image on the left shows the hierarchical levels found in the structural makeup of intermediate filament protein material, from the nano- to the macro-scale. Our work has elucidated the molecular structure and associated deformation mechanisms of intermediate filaments, and enabled a direct comparison between experiment and simulation. Our studies provided a new way forward in carrying out multi-scale studies of structure-property relationships in the intermediate filament protein family, starting from the nanoscale. The use of the new simulation model combined with experimental studies using Atomic Force Microscopy or optical tweezers opens the possibility for probing the effect of mutations using in silico materiomics methods. 

In addition to biomedical applications, intermediate filaments can be considered as a model system that may enable us to fabricate novel nanomaterials that display a high sensitivity to applied forces, show flaw tolerant properties, provide a rapid route towards self-assembly, and combine biological compatibility with the possibility to achieve multifunctional and mutable material properties. We have demonstrated this by the direct simulation of large-scale protein networks of intermediate filaments and a detailed mechanical analysis of failure mechanisms. 

Such nanomaterials could be used as biomaterials for clinical applications, or as novel efficient energy-absorbing materials. Since the molecular structure of intermediate filaments can be converted to beta-sheets upon stretching, bundles of intermediate filaments could potentially be converted into silk-like fibers with similar strength and toughness as spider silk.











Selected publications

Z. Qin, M.J. Buehler, “Structure and dynamics of human vimentin intermediate filament dimer and tetramer in explicit and implicit solvent models,” J. Mol. Model., accepted for publication 

Z. Qin, M.J. Buehler, “ Molecular Dynamics Simulation of the a-Helix to ß-Sheet Transition in Coiled Protein Filaments: Evidence for a Critical Filament Length Scale ”, Physical Review Letters , Vol. 104(19), paper # 198304, 2010 (link to paper...)

Z. Qin, M.J. Buehler, L. Kreplak, “A multi-scale approach to understand the mechanobiology of intermediate filaments”, J. Biomechanics, Vol. 43(1), pp. 15-22, 2010 (link to paper...

R. Kirmse, Z. Qin, C.M. Weinert, A. Hoenger, M.J. Buehler, L. Kreplak, “Plasticity of intermediate filament subunits,” PLoS ONE, Vol. 5(8), paper # e12115, 2010 (link to paper...

J. Bertaud, Z. Qin, M.J. Buehler, “Intermediate filament deficient cells show mechanical softening at large deformation”, Acta Biomaterialia, Vol. 6(7), pp. 2457-2466, 2010 (link to paper...).

Z. Qin, L. Kreplak, M.J. Buehler, “Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments”, PLoS ONE, Vol. 4(10), paper # e7294, 2009 (link to paper...).

Z. Qin, L. Kreplak, M.J. Buehler, “Nanomechanical properties of vimentin intermediate filament dimers”, Nanotechnology, Vol. 20(42), paper # 425101, 2009 (link to paper...).

T. Ackbarow, D. Sen, C. Thaulow, M.J. Buehler, “Alpha-Helical Protein Networks are Self Protective and Flaw Tolerant”, PLoS ONE, Vol. 4(6), paper # e6015, 2009 (link to paper...

T. Ackbarow, M.J. Buehler, “Nanopatterned protein domains unify strength and robustness through hierarchical structures,” Nanotechnology, Vol. 20, paper # 075103, 2009 (link to paper...)

Z. Qin, S. Cranford, T. Ackbarow, M.J. Buehler, “Robustness-strength performance of hierarchical alphahelical protein filaments”, International Journal of Applied Mechanics, Vol. 1(1), 2009 (link to paper...

T. Ackbarow and M.J. Buehler, “Superelasticity, energy dissipation and strain hardening of vimentin coiled-coil intermediate filaments”, J. Materials Science, Vol. 21(11), pp. 2855-2869, 2007 (link to paper...). 

H. Zhang, T. Ackbarow, M.J. Buehler, “Muscle dystrophy single point mutation in the 2B segment of lamin A does not affect the mechanical properties at the dimer level”, J. Biomechanics Vol. 41(6) pp.1295-1301 (link to paper... ).

Research support provided by: ARO, AFOSR, ONR, DARPA, NSF, German Academic Foundation (Studienstiftung des Deutschen Volkes), MIT-Italy Progetta Rocca Program, MIT-Italy MITOR, and others.



Contact us

Laboratory for Atomistic & Molecular Mechanics

Department of Civil and Environmental Engineering

Massachusetts Institute of Technology

Telephone: 617.452.2750

Fax: 617.324.4014



Assistant: Marygrace Aboudou