Regulated dissipation in active mechanobiology

生物材料在物理世界中是独一无二的，因为它们能够以一种精确控制的方式将化学能转化为活性力量。生物相互作用中的这些活跃力量与作用于生物的化学一样重要。与这些主动力同样重要的是传递这些力的机械耦合的相对耗散或弹性；稳定有利于低耗散(创建固体弹性结构)，而运动有利于快速耗散(创建较弱的粘性结构)。尽管对生物系统中产生的力进行了深入的研究，但力与动态机械特性之间的调节关系实际上仍然是未知的。清楚地了解这些关系将为生物学提供一种革命性的方法，在主动机制方面，开启理解和治疗疾病的新战略。此外，表征这些非凡的材料系统将使我们能够重建新的定制的活性材料，这些材料捕捉到与生物相同的丰富的动力学。目标：该计划遵循两个核心目标：(1)识别和表征负责粘弹性行为的分子控制，(2)重新设计体现这些活性材料属性的仿生系统。1：主动机械生物学。这一部分将研究肌动蛋白细胞骨架中的力反馈机制，因为它是一种无处不在的主动结构组件。它将专注于肌动蛋白交联蛋白，如α-肌动蛋白和细丝素，因为动态交联剂被认为是机械松弛和力传感的关键组成部分。2：仿生活性材料。这一组成部分将与目标1的重组系统研究重叠，利用这些机械生物学的发现，但将把它扩展到创造复制类似的细胞活性机制的活性生物材料。这些活性材料将为创造具有可调粘弹性力学并能做机械功的功能材料提供开发平台。意义由于这项拟议研究的广泛性和基础性，预计将对医学、材料科学和生物物理学产生深远影响。从健康的角度来看，破译这些生物力学反应是至关重要的，因为众所周知，组织中的机械变化是许多疾病的关键组成部分。使用机械来制造更简单的诊断工具可能是一个重要的进步；随着发达国家的医疗成本变得令人望而却步，利用机械的简单、廉价的方法将提供必要的替代设备。了解这些机理对于创造新型活性材料至关重要。从史前石器到碳纤维复合材料，历史上的每一个时期都以其复杂的材料为特征。生物的创新已经激发了一系列工程材料的灵感，如尼龙搭扣、“壁虎胶带”和自我修复塑料，然而我们还没有创造出一种可以表现出与几乎每一个动物细胞中的可调僵硬、运动能力和主动收缩相似的行为的材料。这种工程材料将代表一种全新的功能材料类别，在从航空航天到防护设备等不同机械载荷的应用中具有无可估量的价值。该项目的HQP将接受物理、分子生物学和工程方面的尖端技术培训。这种跨学科的环境将确保HQP在当今和未来的就业市场上获得最高质量的培训，掌握备受欢迎的生物技术技能。

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. SignificanceDue 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.