Nano - Rheology of Enzymes

纳米 - 酶的流变学

• 批准号: 1404400
• 负责人: Giovanni Zocchi
• 金额: $ 48.42万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1404400&HistoricalAwards=false
• 关键词: Nano; Rheology; Enzymes

Nontechnical. This project explores the mechanical properties of enzymes, which are, with DNA, the molecules most central to life. Enzymes operate like nano-scale machines complete with moving parts, yet the mechanics of the large molecular deformations they undergo is hardly characterized. The project addresses this knowledge gap. It is based on a unique experimental technique which is revealing unsuspected materials properties of these large but compact molecules. It turns out that enzymes are mechanically similar to 'silly putty' ! By characterizing the surprising materials properties of the molecules of life, the small team, comprising the PI and two graduate students, expands basic knowledge of molecular scale phenomena in a fundamental direction. On the educational side, the graduate students involved in the project acquire a unique perspective and rare, truly interdisciplinary technical skills. They think like physicists, and at the same time are technically competent with the molecular biology techniques necessary to lead the development of a new materials science of biomolecules. Technical. Enzymes are deformable molecules, but what is the dynamics of this remarkable 'softness' ? Armed with a unique experimental tool which allows, for the first time, sub-Angstrom resolution measurements of enzyme deformability, the small research team (comprising the PI and two graduate students) is discovering surprising yet fundamental materials properties of these compact macromolecules. This project aims to characterize the recently discovered viscoelastic mechanical response of the folded enzyme, its physical origin and generality. The proposed measurements specifically address the temperature dependence of the internal dissipation for conformational motion, as well as the origin (surface effect / bulk effect) of this dissipation. The broader goal of the proposed experiments is to develop a continuum mechanics approach to the study of conformational motion. This approach may uncover universal features of the mechanics of enzymes, which are not apparent in the traditional kinetic description. One example is the viscoelastic transition; more generally, these experiments impact our understanding of dissipative dynamics in molecular scale systems. Finally, the PI's aim is to build an understanding of what is general and what is system specific in the mechanics of enzymes and biomolecules generally. This knowledge is essential for the design of modular, artificial molecular control systems.The experimental method ('nanorheology'), invented in the PI's lab, measures the ensemble averaged deformation of the folded state of a protein elicited by an applied oscillatory stress. The technique measures the mechanical susceptibility of the sample molecule in the relevant frequency range (10 Hz - 10 kHz) and for deformations in the relevant sub-Angstrom to sub-nanometer regime.

非技术性的该项目探索酶的机械特性，这些酶与DNA一起是生命最核心的分子。酶的运作就像是一台带有运动部件的纳米级机器，但它们所经历的大分子变形的力学特征却很难描述。该项目解决了这一知识差距。它基于一种独特的实验技术，揭示了这些大而紧凑的分子的未知材料特性。事实证明，酶在机械上类似于“愚蠢的腻子”！通过表征生命分子令人惊讶的材料特性，由PI和两名研究生组成的小团队在一个基本方向上扩展了分子尺度现象的基本知识。在教育方面，参与该项目的研究生获得了独特的视角和罕见的，真正跨学科的技术技能。他们像物理学家一样思考，同时在技术上能够胜任领导生物分子新材料科学发展所必需的分子生物学技术。技术.酶是可变形的分子，但这种非凡的“柔软性”的动力学是什么？配备了一个独特的实验工具，首次允许酶变形性的亚埃分辨率测量，这个小型研究团队（包括PI和两名研究生）正在发现这些紧凑的大分子的令人惊讶的基本材料特性。该项目的目的是表征最近发现的粘弹性机械响应的折叠酶，其物理起源和一般性。建议的测量具体解决温度依赖性的构象运动的内部耗散，以及这种耗散的起源（表面效应/体效应）。拟议的实验的更广泛的目标是开发一个连续介质力学的方法来研究构象运动。这种方法可以揭示酶的力学的普遍特征，这在传统的动力学描述中是不明显的。一个例子是粘弹性转变;更一般地说，这些实验影响了我们对分子尺度系统中耗散动力学的理解。最后，PI的目的是建立一个什么是一般的，什么是酶和生物分子的力学系统具体的理解。这些知识对于模块化人工分子控制系统的设计至关重要。PI实验室发明的实验方法（“纳米流变学”）测量由施加的振荡应力引起的蛋白质折叠状态的整体平均变形。该技术测量样品分子在相关频率范围（10 Hz - 10 kHz）内的机械磁化率，并测量相关亚埃至亚纳米范围内的变形。