Collaborative Research: Dynamics and Stability of Multi-Component Lipid Vesicles in Flow

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

Vesicles are sub-cellular compartments consisting of sacs of fluid enclosed by a lipid bilayer membrane. They play a key role in several cellular processes such as molecular trafficking. Synthetic vesicles are often used in industrial applications such as drug delivery and personal care products. For example, small vesicles (lipid nanoparticles) with mixed-composition membranes have been used to enhance delivery of mRNA vaccines across cell boundaries. Most vesicles of practical importance consist of a bilayer with multiple lipid components and/or proteins that exist either in a well-mixed fluid state or with phase-separated domains enriched in protein. This complex phase behavior plays a major role in concentrating proteins for signaling and membrane budding. However, little is known about how this phase behavior is affected when vesicles are suspended in a flow in physiological situations or in manufacturing processes. Flow-induced deformation affects the phase transitions of such systems due to changes in membrane tension and energetics of lipid rearrangement. This work will provide the first quantitative study of how flow-induced tension alters the thermodynamics and kinetics of lipid domain formation for multicomponent membranes. Results from the project will reveal how vesicle composition affects membrane deformation and breakup in flow, which is becoming increasingly important for manufacturing vesicles in a controlled, high-throughput fashion for biomedical applications including mRNA vaccines. Experiments and boundary element simulations will be used to study the behavior of multicomponent vesicles under precisely defined flows. By directly visualizing vesicles with well controlled compositions inside a microfluidic device known as a Stokes trap, this study will explore how external flow alters the kinetics and thermodynamics of phase separation in multicomponent membranes, and in turn, how these behaviors affect vesicle shape and conformation. Both simulations and experiments will quantify flow instabilities in which thin tethers pull out from vesicle membranes, in addition to providing a clear understanding of how phase separation alters the critical conditions for such instabilities. The simulations will in particular provide quantitative information on how flow-induced deformation, de-mixing, and membrane bending timescales compete to determine the non-uniform stretching of vesicles and the extrusion of tethers. The research team will create events for the Cena y Ciencias program (“Supper and Science”) at Illinois, which brings K-5 students and their families to a monthly science night at local elementary schools to learn about soft materials such as polymers, biomaterials, and organic electronics. At Purdue, science demonstrations will be performed about complex fluids and interfacial science for local elementary school students. These events will be repurposed as exhibits for a local science museum that has 20,000 annual visitors. 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.