A toolkit for transformable materials

How to design materials with reprogrammable shape and function

Harvard researchers have developed a general framework to design reconfigurable metamaterials that is scale independent, meaning it can be applied to everything from meter-scale architectures to reconfigurable nano-scale systems (Image courtesy of Johannes Overvelde/Harvard SEAS).

Metamaterials — materials whose function is determined by structure, not composition — have been designed to

• bend light and sound, 
• transform from soft to stiff, and 
• even dampen seismic waves from earthquakes. 

But each of these functions requires a unique mechanical structure, making these materials great for specific tasks, but difficult to implement broadly.
But what if a material could contain within its structure, multiple functions and easily and autonomously switch between them?

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute of Biologically Inspired Engineering at Harvard University have developed a general framework to design reconfigurable metamaterials. The design strategy is scale independent, meaning it can be applied to everything from meter-scale architectures to reconfigurable nano-scale systems such as photonic crystals, waveguides and metamaterials to guide heat.

The research is published in Nature.

“In terms of reconfigurable metamaterials, the design space is incredibly large and so the challenge is to come up with smart strategies to explore it,” said Katia Bertoldi, John L. Loeb Associate Professor of the Natural Sciences at SEAS and senior author of the paper. “Through a collaboration with designers and mathematicians, we found a way to generalize these rules and quickly generate a lot of interesting designs.”

Bertoldi and former graduate student Johannes Overvelde, who is the first author of the paper, collaborated with Chuck Hoberman, of the Harvard Graduate School of Design (GSD) and associate faculty at the Wyss and James Weaver, a senior research scientist at the Wyss, to design the metamaterial.

The research began in 2014, when Hoberman showed Bertoldi his original designs for a family of foldable structures, including a prototype of an extruded cube. “We were amazed by how easily it could fold and change shape,” said Bertoldi. “We realized that these simple geometries could be used as building blocks to form a new class of reconfigurable metamaterials but it took us a long time to identify a robust design strategy to achieve this.”

The interdisciplinary team realized that assemblies of polyhedra can be used as a template to design extruded reconfigurable thin-walled structures, dramatically simplifying the design process.

“By combining design and computational modeling, we were able to identify a wide range of different rearrangements and create a blueprint or DNA for building these materials in the future, ” said Overvelde, now scientific group leader of the Soft Robotic Matter group at FOM Institute AMOLF in the Netherlands.

The same computational models can also be used to quantify all the different ways in which the material could bend and how that affected effective material properties like stiffness. This way they could quickly scan close to a million different designs, and select those with the preferred response.

Once a specific design was selected, the team constructed working prototypes of each 3D metamaterial both using laser-cut cardboard and double-sided tape, and multimaterial 3D printing. Like origami, the resulting structure can be folded along their edges to change shape.

“Now that we’ve solved the problem of formalizing the design, we can start to think about new ways to fabricate and reconfigure these metamaterials at smaller scales, for example through the development of 3D-printed self actuating environmentally responsive prototypes,” said Weaver.

This formalized design framework could be useful for

• structural and aerospace engineers, 
• material scientists, 
• physicists, 
• robotic engineers, 
• biomedical engineers, 
• designers and 
• architects.

“This framework is like a toolkit to build reconfigurable materials,” said Hoberman. “These building blocks and design space are incredibly rich and we’ve only begun to explore all the things you can build with them.”

This work was supported by the Materials Research Science and Engineering Center and the National Science Foundation.

ORIGINAL: Harvard SEAS
By Leah Burrows
January 18, 2017

DNA nanoswitches reveal how life's molecules connect

A complex interplay of molecular components governs almost all aspects of biological sciences - healthy organism development, disease progression, and drug efficacy are all dependent on the way life's molecules interact in the body. Understanding these bio-molecular interactions is critical for the discovery of new, more effective therapeutics and diagnostics to treat cancer and other diseases, but currently requires scientists to have access to expensive and elaborate laboratory equipment.


Now, a new approach developed by researchers at the Wyss Institute for Biologically Inspired Engineering, Boston Children's Hospital and Harvard Medical School promises a much faster and more affordable way to examine bio-molecular behavior, opening the door for scientists in virtually any laboratory world-wide to join the quest for creating better drugs. The findings are published in February's issue of Nature Methods.

"Bio-molecular interaction analysis, a cornerstone of biomedical research, is traditionally accomplished using equipment that can cost hundreds of thousands of dollars," said Wyss Associate Faculty member Wesley P. Wong, Ph.D., senior author of study. "Rather than develop a new instrument, we've created a nanoscale tool made from strands of DNA that can detect and report how molecules behave, enabling biological measurements to be made by almost anyone, using only common and inexpensive laboratory reagents."

Wong, who is also Assistant Professor at Harvard Medical School in the Departments of Biological Chemistry & Molecular Pharmacology and Pediatrics and Investigator at the Program in Cellular and Molecular Medicine at Boston Children's Hospital, calls the new tools DNA "nanoswitches".

Nanoswitches comprise strands of DNA onto which molecules of interest can be strategically attached at various locations along the strand. Interactions between these molecules, like the successful binding of a drug compound with its intended target, such as a protein receptor on a cancer cell, cause the shape of the DNA strand to change from an open and linear shape to a closed loop. Wong and his team can easily separate and measure the ratio of open DNA nanoswitches vs. their closed counterparts through gel electrophoresis, a simple lab procedure already in use in most laboratories, that uses electrical currents to push DNA strands through small pores in a gel, sorting them based on their shape

"Our DNA nanoswitches dramatically lower barriers to making traditionally complex measurements," said co-first author Ken Halvorsen, formerly of the Wyss Institute and currently a scientist at the RNA Institute at University of Albany. "All of these supplies are commonly available and the experiments can be performed for pennies per sample, which is a staggering comparison to the cost of conventional equipment used to test bio-molecular interactions."

To encourage adoption of this method, Wong and his team are offering free materials to colleagues who would like to try using their DNA nanoswitches.

"We've not only created starter kits but have outlined a step-by-step protocol to allow others to immediately implement this method for research in their own labs, or classrooms" said co-first author Mounir Koussa, a Ph.D. candidate in neurobiology at Harvard Medical School.

"Wesley and his team are committed to making an impact on the way bio-molecular research is done at a fundamental level, as is evidenced by their efforts to make this technology accessible to labs everywhere," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Boston Children's Hospital and Harvard Medical School and a Professor of Bioengineering at Harvard SEAS. "Biomedical researchers all over the world can start using this new method right away to investigate how biological compounds interact with their targets, using commonly-available supplies at very low cost."


ORIGINAL: Physorg.com
Jan 30, 2015

Robotic construction crew needs no foreman

Harvard graduate student Kirstin Petersen (left) and staff scientist Justin Werfel (right) traveled to Namibia to study termite mounds—the inspiration for the TERMES robots that can autonomously build towers, castles, and pyramids out of foam bricks. Credit: Harvard's Wyss Institute

Cambridge, Mass. — On the plains of Namibia, millions of tiny termites are building a mound of soil—an 8-foot-tall "lung" for their underground nest. During a year of construction, many termites will live and die, wind and rain will erode the structure, and yet the colony's life-sustaining project will continue.

Inspired by the termites' resilience and collective intelligence, a team of computer scientists and engineers at the Harvard School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University has created an autonomous robotic construction crew. The system needs no supervisor, no eye in the sky, and no communication: just simple robots—any number of robots—that cooperate by modifying their environment.

Harvard's TERMES system demonstrates that collective systems of robots can build complex, three-dimensional structures without the need for any central command or prescribed roles. The results of the four-year project were presented this week at the AAAS 2014 Annual Meeting and published in the February 14 issue of Science.

The TERMES robots can build towers, castles, and pyramids out of foam bricks, autonomously building themselves staircases to reach the higher levels and adding bricks wherever they are needed. In the future, similar robots could lay sandbags in advance of a flood, or perform simple construction tasks on Mars.

"The key inspiration we took from termites is the idea that you can do something really complicated as a group, without a supervisor, and secondly that you can do it without everybody discussing explicitly what's going on, but just by modifying the environment," says principal investigator Radhika Nagpal, Fred Kavli Professor of Computer Science at Harvard SEAS. She is also a core faculty member at the Wyss Institute, where she co-leads the Bioinspired Robotics platform.

The TERMES robots can carry bricks, build staircases, and climb them to add bricks to a structure, following low-level rules to independently complete a construction project. Credit: Eliza Grinnell, Harvard SEAS

"We try to draw inspiration from the elegant ways in which Nature self organizes and self regulates," said Wyss Institute Founding Director Don Ingber, Ph.D., M.D., "and this latest feat by our robotics team is clear evidence of the tremendous potential of bioinspired engineering, and its ability to spawn truly game-changing technologies."

Most human construction projects today are performed by trained workers in a hierarchical organization, explains lead author Justin Werfel, a staff scientist in bioinspired robotics at the Wyss Institute and a former SEAS postdoctoral fellow.

"Normally, at the beginning, you have a blueprint and a detailed plan of how to execute it, and the foreman goes out and directs his crew, supervising them as they do it," he says. "In insect colonies, it's not as if the queen is giving them all individual instructions. Each termite doesn't know what the others are doing or what the current overall state of the mound is."

Instead, termites rely on a concept known as stigmergy, a kind of implicit communication: they observe each others' changes to the environment and act accordingly. That is what Nagpal's team has designed the robots to do, with impressive results. Supplementary videos published with the Science paper show the robots cooperating to build several kinds of structures and even recovering from unexpected changes to the structures during construction.

The TERMES robots, developed at Harvard, act independently but collectively. Credit: Eliza Grinnell, Harvard SEAS.

Each robot executes its building process in parallel with others, but without knowing who else is working at the same time. If one robot breaks, or has to leave, it does not affect the others. This also means that the same instructions can be executed by five robots or five hundred. The TERMES system is an important proof of concept for scalable, distributed artificial intelligence.

Nagpal's Self-Organizing Systems Research Group specializes in distributed algorithms that allow very large groups of robots to act as a colony. Close connections between Harvard's computer scientists, electrical engineers, and biologists are key to her team's success. They created a swarm of friendly Kilobots a few years ago and are contributing artificial intelligence expertise to the ongoing RoboBees project, in collaboration with Harvard faculty members Robert J. Wood and Gu-Yeon Wei.

"When many agents get together—whether they're termites, bees, or robots—often some interesting, higher-level behavior emerges that you wouldn't predict from looking at the components by themselves," says Werfel. "Broadly speaking, we're interested in connecting what happens at the low level, with individual agent rules, to these emergent outcomes."

Coauthor Kirstin Petersen, a graduate student at Harvard SEAS with a fellowship from the Wyss Institute, spearheaded the design and construction of the TERMES robots and bricks. These robots can perform all the necessary tasks—carrying blocks, climbing the structure, attaching the blocks, and so on—with only four simple types of sensors and three actuators.


Watch a video of the robots in action.

"We co-designed robots and bricks in an effort to make the system as minimalist and reliable as possible," Petersen says. "Not only does this help to make the system more robust; it also greatly simplifies the amount of computing required of the onboard processor. The idea is not just to reduce the number of small-scale errors, but more so to detect and correct them before they propagate into errors that can be fatal to the entire system."

In contrast to the TERMES system, it is currently more common for robotic systems to depend on a central controller. These systems typically rely on an "eye in the sky" that can see the whole process or on all of the robots being able to talk to each other frequently. These approaches can improve group efficiency and help the system recover from problems quickly, but as the numbers of robots and the size of their territory increase, these systems become harder to operate. In dangerous or remote environments, a central controller presents a single failure point that could bring down the whole system.

"It may be that in the end you want something in between the centralized and the decentralized system—but we've proven the extreme end of the scale: that it could be just like the termites," says Nagpal. "And from the termites' point of view, it's working out great."

This research was supported by the Wyss Institute for Biologically Inspired Engineering at Harvard University.

What can a TERMES robot do?
- Move forward, backward, and turn in place
- Climb up or down a step the height of one brick
- Pick up a brick, carry it, and deposit it directly in front of itself
- Detect other bricks and robots in immediate vicinity
- Keep track of its own location with respect to a "seed" brick

What instructions do the TERMES robots follow?
- Obey predetermined traffic rules
- Circle the growing structure to find the first, "seed" brick (for orientation)
- Climb onto the structure
- Obtain a brick
- Attach the brick at any vacant point that satisfies local geometric requirements
- Climb off the structure
- Repeat

ORIGINAL: Wyss Institute for Biologically Inspired Engineering 
Date: Feb 13, 2014

Genome-scale engineering for systems and synthetic biology

ORIGINAL: Nature

Kevin M Esvelt1 & Harris H Wang1,2,a

This paper is part of the series on Systems Biology Technologies. See more papers from this series.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA

Department of Systems Biology, Harvard Medical School, Boston, MA, USA

Correspondence to: Kevin M Esvelt1Harris H Wang1,2,a Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA. Tel.: +1 617 955 9575; Fax: +1 617 432 7828; Email: hw2429@columbia.edu or Tel.: +1 857 919 3375; Fax: +1 617 432 7828; Email: kevin.esvelt@wyss.harvard.edu

Received 21 September 2012; Accepted 16 December 2012; Published online 22 January 2013

aPresent address: Department of Systems Biology, Columbia University Medical Center, 701 West 168th Street, Room 1308-B, New York, NY 10032, USA

Abstract

Genome-modification technologies enable the rational engineering and perturbation of biological systems. Historically, these methods have been limited to gene insertions or mutations at random or at a few pre-defined locations across the genome. The handful of methods capable of targeted gene editing suffered from low efficiencies, significant labor costs, or both. Recent advances have dramatically expanded our ability to engineer cells in a directed and combinatorial manner. Here, we 

• review current technologies and methodologies for genome-scale engineering, 
• discuss the prospects for extending efficient genome modification to new hosts, and 
• explore the implications of continued advances toward the development of 
  • flexibly programmable chasses, 
  • novel biochemistries, and s
  • afer organismal and ecological engineering.

The phrase ‘genome-scale engineering’ invokes a future in which organisms are custom designed to serve humanity. Yet humans have sculpted the genomes of domesticated plants and animals for generations. Darwin’s contemporary William Youatt described selective breeding as ‘that which enables the agriculturalist, not only to modify the character of his flock, but to change it altogether. It is the magician's wand, by means of which he may summon into life whatever form and mold he pleases’ (Youatt, 1837). Selective breeding has transformed aurochs into Holsteins, wolves into Chihuahuas and Great Danes, and teosinte into maize. All of these examples involved genomic changes at a scale dwarfing any attempted through rational design. Understanding why genomes have been more readily shaped by evolutionary principles than conventional design-based approaches is important for current and future genome engineering endeavors.

Engineering is a human enterprise consisting of iterative cycles of design, construction, and testing. Optimizing this iterative process involves balancing the relative time, costs, and expected benefits gained at each phase. However, rationally designing and building a genome to produce the desired phenotype has proven exceedingly difficult. Designing organisms to specification requires accurately predicting phenotype from genotype, a complex problem that is worsened by our incomplete knowledge of biomolecule production, degradation, and interaction rates. Moreover, the computational resources required to run bottom-up molecular-level simulations are daunting even for simpler systems (Karr et al, 2012; Koch, 2012). Nevertheless, models have been useful for generating new hypotheses and targeting promising areas for engineering. Yet, even with the best in silico predictions, we are still limited by our ability to construct the designed genome. More than any other factor, the absence of molecular tools for manipulating genomic sequences has forced us to rely on selective breeding and evolutionary optimization (Conrad et al, 2011) rather than rational genome design.

Recent breakthroughs in genomics and genome editing have promised a greater role for rational design in biological engineering (Figure 1), offering new opportunities for systems and synthetic biologists aiming to reverse-engineer naturally evolved systems and to build new systems. In particular, advances in high-throughput DNA sequencing and large-scale biomolecular modeling of metabolic and signaling networks represent two important new frontiers that aid genome-scale engineering. Over the last few years, thousands of bacterial genomes have been sequenced from a wide variety of natural species and numerous laboratory-generated strains (Pagani et al, 2012). These efforts have illuminated many essential features of the core genome (Lukjancenko et al, 2010), the extent and importance of genetic heterogeneity across populations (Avery, 2006), the ubiquity of horizontal gene transfer (Smillie et al, 2011), and the evolution and selection of functional genetic elements (David and Alm, 2011). At the same time, new computational tools have used the flood of data to model metabolic processes and signaling networks across the entire cell, generating many new testable hypotheses (Lewis et al, 2012). Most importantly, emerging advances in de novosynthesis and in vivo gene targeting allow empirical validation of these model-driven hypotheses. By building and testing synthetic variants of biological systems, we have a unique opportunity to decipher the constraints imposed by the complexity of evolved systems and develop strategies for engineering living systems more conducive to quantitative modeling and rational design.

Figure 1. A historical timeline of selected advances leading to genome-scale engineering.

Here we review recent technologies that empower design-based genome engineering approaches, identify potential bottlenecks, discuss strengths and limitations of strategies employing rational design versus evolution, and consider future applications of genome-scale engineering. We advocate a synergistic engineering strategy that adopts the best aspects of rational genome design and evolutionary optimization.

What is genome-scale engineering?

Genome engineering is the art of constructing a genotype that gives rise to a desired phenotype, a challenge whose difficulty is influenced by the scale of genomic alteration required. One measure of scale is the number of changes that must be made to an existing genome to produce the desired phenotype. In some cases, this may require editing only one gene, a task that is clearly not genome scale. The same is true for a library of single-gene variants and even a complete collection of single-gene knockouts (Giaever et al, 2002; Baba et al, 2006), as each genome has only a single change. We define genome-scale engineering to be any endeavor involving sequence modifications to at least two distinct regions of a genome. In what follows, we will mainly focus on technologies potentially capable of modifying large fractions of a single genome.

Genome-scale engineering allows us to experimentally probe deep biological questions such as essentiality (Koonin, 2000), epistasis (Chou et al, 2011; Khan et al, 2011), encoding (Itzkovitz and Alon, 2007), evolvability (Tokuriki and Tawfik, 2009; Wagner and Zhang, 2011;Hill and Zhang, 2012), and robustness (Bershtein et al, 2006). At the same time, we aim to rationally build useful organisms that cannot be easily generated by harnessing evolution alone. Such endeavors require foundational tools in design, modeling, construction, and testing that extend from individual cells to populations of organisms (Figure 2). Iterations of design, model, build, and test phases are likely to be more important as the scale of the endeavor increases because biological complexity can grow exponentially. Below, we describe key features of these phases in genome-scale engineering, outline current capabilities, and suggest opportunities for improvement.

Figure 2. Foundational genome engineering tools and approaches are needed to extend single site genetic perturbations of a single genome to multiple changes across many genomes.

Genome designs and models

Design is a set of specifications intended to achieve a dedicated objective under various constraints. Biological designs are those that describe the underlying blueprint of living organisms, built upon the information encoded in genes across the genome. As the focus of biological engineering shifts from individual genes to entire genomes, there is a growing need for more sophisticated genome design tools to assist such large-scale engineering endeavors. Recordkeeping software is essential for tracking numerous modifications designed and generated across libraries of genomes. Traditional gene editors such as Vector NTI and SeqBuilder are largely inadequate for such purposes. However, new design tools and software suites such as J5 (Hillson et al, 2012), Clotho (Xia et al, 2011), and Genome Compiler (http://www.genomecompiler.com/) provide better data management and user interfaces for the design of large operons and whole genomes.

Writing Messages With Water

ORIGINAL: Tech News Daily

By Julian Taub, 

December 04 2012 05:53 PM ET

Examples of hydroglyphic writing. 

CREDIT: Wyss Institute for Biologically Inspired Engineering

Scientists have used nanotechnology to create “selectively wet” materials that can be used to write long-lasting messages with water.

The concept, called "hydroglyphics," was exhibited by scientists at Harvard who recently teamed up with a group of Merrimack, N.H., high school students and faculty to make an educational demo. 

The demo, appropriately entitled "Hydroglyphics," helps people visualize the difference between water repelling and wetting surfaces. The main principle behind hydroglyphics (a combination of the words “hydro” and “hieroglyphics”) is that by changing the properties of a surface, you can make your own special prints using water. All you need is some foam stickers, a modified Tesla coil and a Petri dish.

[VIDEO: Nanotechnology's Big Impact]

Each audience member takes a Petri dish and chooses a favorite sticker, tacking it onto the bottom of the dish. The demo performer then puts each dish under the Tesla coil, and zaps them. A purple spark appears accompanied by a loud noise. Once the sticker is removed, water is added to the dish. The water fills up everywhere except on the area where the sticker had been, creating an “engraving.” The message can last about one month.

Harvard scientist Philseok Kim, the first author on the paper about this demo, stumbled upon the idea for hydroglyphics. While helping one of Merrimack’s teachers, Raymond Sleeper, come up with a new demo, he experimented with equipment in the lab that was being used for other research projects.

“I tested [the demo on] a Petri dish, to see how much contrast between hydrophilicity and hydrophobicity we could make,” Kim, of the Wyss Institute, said. “To our surprise, it nicely generated strikingly good contrast.”

The Petri dishes originally have a plastic structure that repels water (hydrophobic). When treated with the Tesla coil, the air becomes conductive and oxygen combines with the plastic, making the Petri dish surface attracted to water (hydrophilic). However, the area under the sticker was protected from the air, so it still repels water. Water in the dish sticks to the hydrophobic regions, keeping the message area dry. 

The hydroglyphics demo has been a success wherever the researchers have taken it, Kim said. “Purple electric arcs with funny zapping noise, cute and colorful stickers, and mystery messages… all of them are a series of 'wow' moments that just happen over a few minutes. I think this is a truly engaging combination.”

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