Regulated dissipation in active mechanobiology

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Biological materials are unique in the physical world in that they are able to convert chemical energy into active forces in a precisely controlled way. These active forces in biological interactions are as critical as the chemistry acting on biology. Equally as important as these active forces are the relative dissipation or elasticity of the mechanical couplings that transmit these forces; while stability favors low dissipation (creating solid elastic structures), movement favors rapid dissipation and (creating weaker viscous structures). **Despite intensive efforts to characterize the forces generated in biological systems, the regulatory relationships between forces and dynamic mechanical properties remain virtually unknown. A clear picture of these relationships would provide a revolutionary approach to biology in terms of active mechanics, opening new strategies to understand and treat disease. Moreover, characterizing these remarkable material systems will allow us to recreate new tailored active materials that capture the same rich dynamics as biology.**Objectives:*This program follows two core goals : (1) identify and characterize the molecular controls responsible for viscoelastic behavior, and (2) reengineer biomimetic systems which embody these active material properties. **1: Active Mechanobiology. This component will examine the force-feedback mechanics in the actin cytoskeleton, as it is a ubiquitous active structural component. It will focus on actin crosslinking proteins, such as alpha-actinin, and filamin, as dynamic crosslinking is believed to be a key component in mechanical relaxation, and force-sensing. **2: Biomimetic active materials. This component will overlap with the reconstituted systems studies of Objective 1, capitalizing on these discoveries of mechanobiology, but will extend it to create active biomaterials that reproduce similarly active mechanics of cells. These active materials will provide a development platform for creating functional materials that have tunable viscoelastic mechanics and can do mechanical work. **Significance*Due to the broad and fundamental nature of this proposed research, far-reaching impact in medicine, materials science, and biophysics are anticipated. From a health perspective, it is essential to decipher these biomechanical responses, as mechanical changes in tissue are known to be a key component of many diseases. Using mechanics as a way to make simpler diagnostic tools may be an essential advance; as healthcare costs in the developed world become prohibitive, simple, inexpensive approaches that exploit mechanics will provide essential alternative devices. **Understanding these mechanics is critical for creating novel active materials. Every period in history has been characterized by its sophistication of materials, from prehistoric stone tools to carbon fiber composites. Biology's innovation, has already inspired a broad range of engineered materials such as Velcro, "Gecko tape" and self healing plastics, yet we have not created a material that can display behavior remotely similar to the tunable stiffness, capacity for movement, and active contractility found in virtually every animal cell. Such an engineered material would represent an entirely new class of functional materials, invaluable in applications subjected to varying mechanical loads, from aerospace to protective equipment.**HQP in this program will be trained in cutting edge techniques in physics, molecular biology, and engineering. This interdisciplinary environment will ensure that HQP have the highest quality training in highly sought-after biotechnology skills in today's and tomorrow's job markets.