CAREER: Dynamics of cells and celullar mimetics in flow and electric fields: An integrated biophysical and engineering approach

0846247 p。可变形微观结构与宏观尺度流动动力学之间的相互作用是颗粒和多相流体动力学中一个长期存在的问题。主要的挑战来自粒子界面的自由边界性质。包裹细胞的脂质双层膜由于其独特的力学特性，是一个特别复杂的界面：分子薄膜是一个高度柔性的不可压缩的液体片。因此，由封闭的脂质双分子层（细胞和囊泡）组成的颗粒比胶囊和滴状物表现出更丰富的动力学。本研究的目的是了解流体-双层膜耦合，长期目标是解释软颗粒悬浮液（如生物细胞）的非平衡动力学。为了实现这些目标，PI将整合流体动力学和生物物理学的思想，建立一个统一的理论框架，以阐明膜变形和组成、流体运动和外场之间的相互关系。这种变革性的方法包括三个基本的非平衡问题：流动、电场和多组分膜。所提出的理论、数值和实验相结合的工作将量化囊泡在外场中的变形、取向和运动。智力优势：本职业规划提出了非平衡双分子层膜的第一个系统研究。提出的研究将促进我们对纳米尺度（例如，膜热波动，穿孔），微观尺度（例如，单个囊泡变形）和宏观尺度（例如，囊泡悬浮液的流变学）物理过程相互作用的理解。此外，它将阐明几个有争议的话题，例如，线性和复杂流动中囊泡行为的多样性，电场中囊泡的不寻常形状，以及囊泡悬浮液的粘度。更广泛的影响：该研究结果将在多个方向上极大地推动生物仿生领域的发展。首先，新知识将为由脂质双层构建的微纳米器件的创新设计奠定坚实的基础，例如纳米管网络和囊泡容器。其次，拟议的研究将揭示细胞力相互作用的新一般特征，这可能会影响广泛的应用，包括细胞电操作和靶向药物和基因传递。该项目具有很强的跨学科性质，结合了许多领域的基础知识，包括生物学、物理学和工程学。由PI发起的国际和跨学科合作将促进不同研究和地理区域的科学家和工程师之间的交流。作为一名女性教员，PI将作为达特茅斯女性参与科学项目的一部分，成为女性的导师和榜样，并将接触到其他在科学和工程领域未被充分代表的少数族裔。她将与蒙特希尔科学博物馆和达特茅斯外联办公室合作，为贫困和农村地区资源不足的学校制定教育计划。教育。PI将开发新的课程，例如细胞和分子生物力学，它融合了工程和生物物理学。这些课程将加强达特茅斯学院的课程设置，该学院在复杂生物系统方面的工程研究和教育正处于起步阶段。PI的教学将强调分析技能和理论框架在解决学生在职业生涯中遇到的现实问题中的重要性。她正在联合组织一个“复杂和生物流体流动”的暑期学校，讲座将在网上发布，以促进学科之间和代际之间的知识转移。这位PI将在每年的塞耶工程学院开放日上展示她的实验室，向公众宣传科学之美，该开放日吸引了儿童、他们的家人和当地的工程爱好者。

0846247P. VlahovskaThe interplay between deformable microstructure and macroscale flow dynamics is a long-standing problem in particulate and multiphase fluid dynamics. The major challenge stems from the free-boundary nature of the particle interface. Lipid bilayer membranes that envelop cells are particularly complex interfaces because of their unique mechanics: the molecularly thin membrane is a highly-flexible incompressible uid sheet. As a result, particles made of closed lipid bilayers (cells and vesicles) exhibit richer dynamics than would capsules and drops. The objective of the proposed research is to understand the fluid-bilayer membrane coupling, with the long-term goal of explaining the non-equilibrium dynamics of suspensions of soft particles, such as biological cells. To achieve these goals, the PI will integrate ideas from fluid dynamics and biophysics to build a unified theoretical framework that will elucidate the interrelation between membrane deformation and composition, fluid motion, and external fields. This transformative approach encompasses three fundamental non-equilibrium problems: flows, electric fields, and multicomponent membranes. The proposed combination of theoretical, numerical, and experimental work will quantify vesicle deformation, orientation, and motion in external fields.Intellectual Merit: This CAREER plan sets forth the first systematic study of non-equilibrium bilayer membranes. The proposed research will advance our understanding of the interplay of physical processes at the nano-scale (e.g., membrane thermal undulations, poration), micro-scale (e.g., single vesicle deformation), and macro-scale (e.g., rheology of vesicle suspensions). Moreover, it will shed light on several controversial topics, e.g., the diversity of vesicle behaviors in linear and complex flows, the unusual shapes of vesicles in electric fields, and the viscosity of vesicle suspensions.Broader Impacts:The outcomes of the research will dramatically advance the field of biomicrouidics in multiple directions. First, the new knowledge will establish a sound basis for innovative designs of micro- and nano-devices built from lipid bilayers, such as networks of nanotubes and vesicle containers. Second, the proposed studies will uncover new general features of cell-force interactions, which will likely impact a wide range of applications, including cell electro-manipulation and targeted drug and gene delivery. The project has a strong interdisciplinary nature and combines fundamental knowledge across many fields, including biology, physics, and engineering. The international and interdisciplinary collaborations initiated by the PI will facilitate communication among scientists and engineers in different research and geographic areas. As a female faculty member, the PI will serve as a mentor and a role model to women as part of the Women in Science Project at Dartmouth, and will reach out to other under-represented minorities in science and engineering. She will collaborate with the Montshire Science Museum and Dartmouth's Outreach Office to develop educational programs for under-resourced schools in poor and rural areas. Education. The PI will develop new courses, e.g., Cellular and Molecular Biomechanics, which fuse engineering and biophysics. Such classes will enhance the curriculum at Dartmouth College, where engineering research and education in complex biological systems is in its early stages. The PI's teaching will emphasize the importance of analytical skills and theoretical framework in solving the real-world problems that students will encounter in their professional lives. She is co-organizing a summer school on Complex and Bio-Fluids Flows," for which the lectures will be web-published, to promote the transfer of knowledge between disciplines and generations. The PI will educate the public about the beauty of science by showcasing her Lab at the annual Thayer School of Engineering open house, which attracts children, their families, and local engineering enthusiasts.