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

Brown University, Providence RI

Investigators

Abstract

0846247 P. Vlahovska The 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.