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

这个学院早期职业发展计划(Career)项目将创建细胞如何改变其形状以响应外力的新模型。该项目将包括设计一种用于向细胞施力的双向仪器--一种将可伸缩的支撑面与可接触细胞表面暴露部分的可移动探头相结合的仪器。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获得精确的应力和应变轨迹。该奖项将促进全民健康，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来研究细胞在外力作用下经历的生化和机械变化，以及一种潜在的诱导所需细胞行为的工具，例如用于生物材料的合成。综合的教育和推广活动包括开发纳米定位和纳米生物力学的新课程，以及关于在农业中使用纳米生物力学方法的推广计划。机械传递是活细胞对外部机械刺激的感知、传递和反应的过程。它对维持正常的细胞、组织和器官功能是必不可少的。该项目将建立一套工具来感知和模拟细胞力学转导动力学和3D动态结构，以实现细胞行为操纵。该项目的具体目标是：(1)建立一个双向的机械传递表征方案，首次使用扫描探针显微镜和动态底物刺激，并在生物力学定量中同步光学和生物力学量化；(2)创造一种新的最优激励力设计技术，将线性孔弹性和非线性时变粘弹性模型用于机械传递动力学的识别；以及(3)结合基于迭代学习的控制和模型预测控制方法，制定一种接近实时的精确跟踪控制算法，以实现对变化的操纵力的高效跟踪，以最大限度地减少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智力优势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.