CAREER: Understanding the Deformability of Biological Filaments from their Atomistic Level Details

职业：从原子级细节了解生物丝的可变形性

• 批准号: 2145615
• 负责人: Sachin Goyal
• 金额: $ 50万
• 依托单位: University of California - Merced
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2145615&HistoricalAwards=false
• 关键词: CAREER; Understanding; Deformability; Biological; Filaments

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).This Faculty Early Career Development (CAREER) award supports research to examine how the mechanical deformability of biological filaments is influenced by the atom-level details of their chemical structures. Biological filaments include those that form our genetic material and make up biological tissues. Understanding how biological filaments deform is important for both bioengineering and medicine. Eventually, this work may enable scientists to manipulate biological filaments to improve the functional ability of the filaments. For example, manipulating mechanical and chemical signals of genetic material can transform gene therapy, or eventually lead to a new treatment for cancer. This work will also transform the way engineering students learn mechanics of materials. It will also bring a radically new perspective basic mechanics questions, such as "Is it possible to obtain a whole range of deformation behaviors by simply changing the atomistic configurations?" This work will create fundamental knowledge that connects the fields of engineering and technology with basic science and mathematics. It will provide primary and high school students a unique learning perspective and empowers schoolteachers with new knowledge on the topics covered under "From Molecules to Organisms: Structures and Processes." The existing models for simulating the deformations of filaments employ linear constitutive laws that are inadequate to explain the crucial mechanics of their biologically relevant deformations. The goal of this research is to clear this roadblock by developing an inverse approach with a rod model framework for estimating the constitutive laws of thin filaments from the data obtained from their all-atom simulations and physical experiments. The related research objectives include: (i) analysis of how the spatial configuration of atoms as well as the bond potentials individually influence the constitutive laws; (ii) development of educational tools and virtual labs for engineering students to learn the mechanics of beams along with some novel concepts. Some of the fundamental questions that will be answered include: (1) how base-pair sequence of the non-coding segments of the genetic filament influences their structural deformability that govern gene expression; (2) how one can design a filament to have a certain constitutive behavior by changing its atomistic structure.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项是根据2021年《美国救援计划法》（公法117-2）全部或部分资助的。本学院的早期职业发展（职业）奖支持研究，以研究生物学细丝的机械变形性如何受其化学结构的原子水平细节的影响。生物丝包括形成我们遗传物质并组成生物组织的细丝。 了解生物丝变形对于生物工程和医学都很重要。最终，这项工作可能使科学家能够操纵生物丝以提高细丝的功能能力。例如，操纵遗传物质的机械和化学信号可以改变基因治疗，或最终导致对癌症的新疗法。这项工作还将改变工程学生学习材料机制的方式。它还将带来一个彻底的新观点基本技工问题，例如“可以通过简单地改变原子配置来获得一系列变形行为吗？”这项工作将创造基本知识，将工程和技术领域与基础科学和数学联系起来。它将为小学和高中生提供独特的学习观点，并使学校老师能够对“从分子到有机体：结构和过程”所涵盖的主题提供新的知识。现有的模拟细丝变形的模型采用线性本构定律，这些定律不足以解释其生物学相关变形的关键力学。这项研究的目的是通过使用Rod模型框架开发反向方法来清除此障碍，该框架从其全部原子模拟和物理实验中获得的数据估算细丝的本构定律。相关的研究目标包括：（i）分析原子的空间构型以及键势如何单独影响本构定律； （ii）开发工程专业学生的教育工具和虚拟实验室，以学习梁的机制以及一些新颖的概念。将要回答的一些基本问题包括：（1）遗传细丝的非编码段的基本对序列如何影响其控制基因表达的结构可变形性； （2）如何通过更改其原子结构来设计灯丝以具有某种构成行为。该奖项反映了NSF的法定任务，并认为使用基金会的知识分子优点和更广泛的影响评估标准，认为值得通过评估来获得支持。