CAREER: Modeling and Control of Cellular Response to Dynamic Mechanical Manipulation Using a Dual-Input Platform

这个教师早期职业发展计划（CAREER）项目将创建细胞响应外力改变形状的新模型。该项目将包括一个双向仪器的设计，用于向细胞施加力-一个结合了一个可以膨胀和收缩的支撑表面，以及一个可以接触细胞表面暴露部分的可移动探针。基于新模型的控制算法将使科学家和工程师能够在整个细胞以及细胞内部的特定细胞器上实现精确的应力和应变轨迹。该奖项将促进国民健康，促进生物科学的进步。它将为细胞生物学家提供一种新的工具，用于研究细胞在外力作用下发生的生物化学和机械变化，以及诱导所需细胞行为的潜在工具，例如，用于合成生物材料。综合教育和外展活动包括开发纳米定位和纳米生物力学的新课程，以及在农业中使用纳米生物力学方法的外展方案。它对维持正常的细胞、组织和器官功能至关重要。本项目将建立一套工具来感知和模拟细胞的机械传导动力学和三维动态结构，以实现细胞行为操纵。本项目的具体目标是：（1）建立双向力学传导表征方案，首次将扫描探针显微镜和动态基底刺激相结合，并将光学和生物力学定量相结合用于生物力学定量;（2）创造一种新的最佳激振力设计技术，以结合并允许线性孔隙弹性和非线性时间-在机械转换动力学的识别中使用的不同粘弹性模型;以及（3）通过结合迭代学习和跟踪迭代，制定近实时精确跟踪控制算法，以实现对变化的操纵力的高效跟踪，从而最小化初始跟踪误差和跟踪迭代。该奖项反映了NSF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 Faculty Early Career Development Program (CAREER) project will create new models of the way that cells change their shape in response to external forces. The project will include the design of a dual-direction instrument for applying forces to cells -- one that combines a supporting surface that can expand and contract, together with a movable probe that can contact exposed portions of the cell surface. A control algorithm based on the new models will allow scientists and engineers to achieve precise stress and strain trajectories across the cell, and on specific organelles in the cell interior. This award will advance the national health, and promote the progress of the biological sciences. It will provide cell biologists with a new tool for studying the biochemical and mechanical changes that cells undergo in response to external forces, as well as a potential tool for inducing desired cell behaviors, for example, for the synthesis of biomaterials. Integrated educational and outreach activities include the development of new courses in nano-positioning and nano-biomechanics, and an outreach program on the use of nano-biomechanical methods in agriculture.Mechanotransduction is the process of sensing, transmission and response to external mechanical stimuli of living cells. It is essential for maintenance of normal cell, tissue, and organ functioning. This project will build a suite of tools to sense and model cellular mechanotransduction dynamics and 3D dynamic structure, in order to achieve cellular behavior manipulation. The specific objectives of this project are to: (1) build a dual-direction mechanotransduction characterization scheme, which for the first time, uses both scanning probe microscopy and dynamic substrate stimuli and synchronizes optical and biomechanical quantification in biomechanical quantification; (2) create a new optimal excitation force design technique to incorporate and allow linear poroelasticity and nonlinear time-varying viscoelasticity models to be utilized in identification of mechanotransduction dynamics; and (3) formulate a near real-time precision tracking control algorithm to achieve high-efficiency tracking of the varying manipulation force to minimize the initial tracking error and tracking iterations by combining both iterative learning-based control and model predictive control approaches.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.