Regulated dissipation in active mechanobiology

主动力学生物学中的调节耗散

• 批准号: RGPIN-2014-05843
• 负责人: Ehrlicher, Allen
• 金额: $ 2.19万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=638072
• 关键词: Regulated; dissipation; active; mechanobiology

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.

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主动力。生物相互作用中的这些积极力量与作用于生物的化学作用一样重要。与这些主动力同样重要的是传递这些力的机械联轴器的相对耗散或弹性；稳定有利于低耗散（形成固体弹性结构），运动有利于快速耗散和（形成较弱粘性结构）。尽管对生物系统中产生的力进行了大量的研究，但力与动态力学特性之间的调节关系仍然是未知的。这些关系的清晰图景将提供一种革命性的主动机制生物学方法，开启理解和治疗疾病的新策略。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活性材料，这些活性材料可以捕获与生物学相同的丰富动态。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特性的仿生系统。1：主动机械生物学。这部分将检查肌动蛋白细胞骨架的力反馈机制，因为它是一个无处不在的活性结构成分。它将专注于肌动蛋白交联蛋白，如α -肌动蛋白和丝蛋白，因为动态交联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。该部分将与目标1的重组系统研究重叠，利用这些机械生物学的发现，但将其扩展到创造活性生物材料，以复制类似的细胞活性力学。这些活性材料将为创造具有可调粘弹性力学和可以做机械功的功能材料提供一个开发平台。由于这项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的影响。从健康的角度来看，破译这些生物力学反应是至关重要的，因为组织中的力学变化是许多疾病的关键组成部分。使用机制创造更简单的诊断工具可能是一种重要的进步；随着发达国家的医疗成本变得令人望而却步，利用机械原理的简单、廉价的方法将提供必要的替代设备。了解这些机制对于创造新的活性材料至关重要。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材料的复杂性为特征。生物学的创新，已经激发了广泛的工程材料，如魔术贴、“壁虎带”和自愈塑料，但我们还没有创造出一种材料，可以显示出与几乎所有动物细胞中可调节的刚度、运动能力和主动收缩性相似的行为。这种工程材料将代表一种全新的功能材料，在从航空航天到防护设备等各种机械载荷的应用中具有不可估量的价值。本项目的HQP将接受物理、分子生物学和工程方面的前沿技术培训。这种跨学科的环境将确保HQP在当今和未来的就业市场上拥有最受欢迎的生物技术技能的最高质量培训。