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

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。该学院早期职业发展（Career）奖支持研究生物细丝的机械可变形性如何受到其化学结构的原子水平细节的影响。生物细丝包括那些形成我们的遗传物质和构成生物组织的细丝。了解生物细丝如何变形对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细丝来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，或最终导致癌症的新治疗方法。这项工作也将改变工程专业学生学习材料力学的方式。它也将带来一个全新的视角，基本的力学问题，如“是否有可能通过简单地改变原子构型来获得一系列的变形行为？”这项工作将创造将工程和技术领域与基础科学和数学联系起来的基础知识。它将为中小学生提供一个独特的学习视角，并赋予学校教师关于“从分子到有机体：结构和过程”主题的新知识。现有的模拟细丝变形的模型采用线性本构定律，不足以解释其生物相关变形的关键力学。本研究的目标是通过开发一种具有杆模型框架的逆方法来清除这一障碍，该方法用于从全原子模拟和物理实验中获得的数据估计细丝的本构定律。相关的研究目标包括：(i)分析原子的空间构型和键势如何单独影响本构律；（ii）开发教学工具和虚拟实验室，让工程学生学习梁的力学以及一些新颖的概念。将回答的一些基本问题包括：(1)遗传丝的非编码片段的碱基对序列如何影响其控制基因表达的结构可变形性；(2)如何通过改变灯丝的原子结构来设计具有某种本构行为的灯丝。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.