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1 Introduction Research in biomolecular materials and processes can contribute to the under- standing of nature and can advance technology in areas of importance to the nation’s health and security. The relevance of these materials and processes to national challenges means that vigorous pursuit of this research is likely to pay sub- stantial dividends not only for U.S. economic competitiveness and well-being but also for its intellectual leadership. In this report, only a few of the many examples of such research were selected for elaboration. This chapter begins by describing some of the concepts that appear throughout the report and subsequently describes current research in four areas. This research is detailed in Chapters 2 and 3 of the report. Finally, a brief summary of enabling tools for research in biomolecular materials is presented. Enabling tools are described in more detail in Chapter 4 of the report. UNIFYINg CONCEPTS There are a number of concepts whose detailed understanding would advance many of the research areas described in this report. The Committee on Biomo- lecular Materials and Processes refers to them here as unifying concepts. Scientific understanding of how systems behave far from equilibrium, how complex systems are controlled via feedback regulation, how they exploit or avoid stochastic effects, and the nature of intermolecular forces remains primitive. Their elucidation would greatly help in the development of biomolecular materials. For example, scientists have a good theoretical understanding of systems at or near equilibrium, yet liv- 

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insPired biology  by ing biological systems function far from equilibrium; in fact, a biological system is at equilibrium only when it is dead! A theory of systems far from equilibrium is needed to understand biological systems properly. Another key concept is control via feedback regulation. The functional precision of biological systems often relies on feedback regulation. Further, many biological processes (and nanoscale devices) involve small numbers of molecules, and the behavior of such systems is influenced in important ways by stochastic fluctuations. The average response often does not mean much. Biological systems have developed mechanisms to take advantage of stochastic fluctuations as well as to quench their effects, in ways that scientists are just beginning to understand. Even our understanding of electrostatics and solvation, the underlying forces that govern the action and interaction of charged molecules in polar media, still relies on decades-old approximations or on lessons from necessarily simplified computer simulations. Until all such forces can be accurately computed and com- bined, scientists will not have a detailed understanding of the action of water and simple ions on intricately constructed macromolecules, much less of the more complex interactions that occur in biological systems. AREAS FOR RESEARCH Alternative and Renewable Energy Harvesting Light The recently achieved molecular-level understanding of photosynthetic mecha- nisms has allowed scientists to create membranes that mimic the essential energy- harnessing properties of natural photosynthesis. A deeper understanding of the structure and function of the photoreaction center of biological systems is inspir- ing the design of synthetic materials and systems that are even more efficient than those found in nature. Fuels Cellulose is the world’s most abundant biological polymer. Its use as a fuel feedstock to create ethanol is one way to reduce the release of carbon dioxide into the atmosphere, since the carbon dioxide formed during combustion is balanced by that absorbed as ethanol-producing plants grow. Cooperative research exploiting advances in plant genetics, process chemistry, biochemistry, chemical biology, and engineering will make it possible to convert renewable biomaterials like cellulose to useful fuels like ethanol.

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introduction  Motors From the subcellular level to the level of the whole body, movement is made possible by proteins that transform chemical to mechanical energy. For many years now there has been the hope of creating synthetic systems capable of similar efficiency and control. Now that we are able to measure force and motion at the molecular level and now that the structure of the component proteins has been resolved, it may soon be possible to mimic these living structure and motility sys- tems to create robust artificial devices such as molecular sorters, filters, concentra- tors, switches, and power sources. Health and Medicine Clinical Diagnostics The ability to diagnose major diseases has improved dramatically in the past two decades. Biomolecular materials have been key to these advances. It is now possible to design biomolecular materials that undergo large physical changes when they bind to a target molecule and to design systems that exploit the consequences of cooperative binding events. Drug Delivery There has been a longstanding interest in using biomolecular materials for the delivery of therapeutic agents. Nanometer-size particles show promise as vehicles for the targeted delivery of payloads such as siRNA and DNA and as labels to monitor such delivery. Prosthetics The design, fabrication, and integration of functional biomaterials into pros- thetic devices present a number of challenges. Next-generation prostheses will likely incorporate feedback loops that involve sensing and actuating components. National Security Sensors Cells can detect minute amounts of molecules with extraordinary sensitivity. However, because only very small physical changes occur when a sensor binds to its target, the problem has been translating such an event into a measurable

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insPired biology  by output signal. Current research on designer biological sensors whose physical states change significantly when they bind to their target may solve this problem. A specific challenge will be to create a sensor that detects engineered as opposed to natural threats. Next-generation Bioinspired Materials Supermaterials Biology presents many examples of materials able to work under extraordinary conditions. The mechanisms that allow geckos to walk on a ceiling and lotus leaves to be self-cleaning are being revealed, as are many of the mechanisms used by other smart biological materials. These revelations may allow scientists and engineers to synthesize improved materials for specific applications. Materials with Information Content Modern polymeric materials serve mainly structural purposes—as plastics, clothing, paints and surface coverings, for example. They are mainly composed of repeats of a single type of monomer unit. The future will see materials that mimic the more flexible sequence-structure-property relationships of biopolymers. Self-evolving, Self-healing, and Self-replicating Materials Populations of living organisms sometimes seem to reengineer themselves, evolving to meet new challenges. Likewise, individuals can adapt to environmental pressures. Current research is aimed at understanding these strategies. Scientists and engineers may someday be able to use these strategies to develop new materials that correspondingly mimic the ability to evolve and adapt. Enabling Tools The exciting current state of research in biomolecular processes and materials has been powered by new experimental and computational tools for interrogating complex systems at a high level of detail. Further advances in the development and application of these tools are crucial to the advancement of the field.

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introduction  Experimental Probes Advances in experimental technologies may soon allow the imaging of cells at the angstrom scale with subsecond resolution. The measurement of forces and motions of nanomachines and the study of the assembly of complex functional structures have also been dramatically advanced. Further development of single- molecule imaging technologies, electron microscopy, and X-ray and neutron scat- tering will be very important. Theoretical and Computational Probes Theory and computation have a rich and proud history in the physical and engineering sciences. A grand success of theory in the life sciences was the deter- mination of the structure of DNA, which emerged from the confluence of theory, computation (wooden models), and diffraction experiments. Today, theory and computation are slowly emerging as an important complement to experimenta- tion in many areas of the biological sciences. However, for theory and computation to become full partners with experiment, significant advances are needed. Such advances would include ways to sample configuration space and dynamic rare events, efficient algorithms for stochastic simulation of spatially resolved coopera- tive dynamic events, and the creation of a fundamental theory of systems far from equilibrium. Chemical Synthesis Researchers have achieved great mastery over small-molecule organic synthesis and characterization. However, at the macromolecular scale, researchers have not gained a corresponding level of synthetic control. Fully characterizing the struc- ture of multifaceted three-dimensional architectures is also currently problematic, yet the solution is of the utmost importance for accurately mapping structure to function. At the most fundamental and essential level, materials researchers must acquire the ability to synthesize, modify, and manipulate novel macromolecules with atomic-level control.