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

0846247P.Vlahovska变形微观结构和宏观流动动力学之间的相互作用是颗粒和多相流体动力学中的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因其独特的机制而特别复杂的界面：分子薄的膜是高度灵活的不可压缩的uid薄片。因此，由封闭的脂质双层(细胞和囊泡)制成的颗粒比胶囊和液滴表现出更丰富的动力学。这项研究的目的是了解流体-双层膜耦合，长期目标是解释生物细胞等软颗粒悬浮液的非平衡动力学。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，阐明膜变形与组成、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。拟议的理论、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。智力上的优点：这份职业生涯计划提出了第一个系统的非平衡双层膜研究。拟议的研究将促进我们在纳米尺度(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)上对物理过程相互作用的理解。此外，它还将阐明几个有争议的话题，如线性和复杂流动中囊泡行为的多样性，电场中囊泡的异常形状，以及囊泡悬浮液的粘度。广泛的影响：该研究的结果将极大地推动生物医学领域向多个方向发展。首先，这一新知识将为创新设计由脂质双层构建的微纳设备奠定坚实的基础，例如纳米管和囊泡容器的网络。其次，拟议的研究将揭示细胞-力相互作用的新的一般特征，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输送。该项目具有很强的跨学科性质，并结合了许多领域的基础知识，包括生物学、物理学和工程学。由国际和平研究所发起的国际和跨学科合作将促进不同研究和地理领域的科学家和工程师之间的交流。作为一名女性教员，PI将作为达特茅斯大学女性科学项目的一部分，充当女性的导师和榜样，并将接触到科学和工程领域其他代表性不足的少数族裔。她将与蒙特郡科学博物馆和达特茅斯外展办公室合作，为贫困和农村地区资源不足的学校开发教育项目。教育。PI将开发融合工程学和生物物理学的新课程，如细胞和分子生物力学。这些课程将加强达特茅斯学院的课程，该学院复杂生物系统的工程研究和教育还处于早期阶段。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活中遇到的现实问题方面的重要性。她正在联合组织一个关于复杂和生物流体流动的暑期学校，讲座将在网上发布，以促进学科和世代之间的知识转移。PI将通过在一年一度的塞耶工程学院开放日上展示她的实验室来教育公众科学的美，该开放日吸引了孩子们、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.