Leveraging Soft Matter Flows across Length Scales to Improve Human Health

Aditya Raghunandan, Mechanical, Aerospace & Nuclear Engineering (MANE) department at Rensselaer Polytechnic Institute (RPI)

Hopeman 224

Across length-scales, the flow of soft biological matter – within the human body or in biomanufacturing — has a profound effect on our health. In this talk, I will focus on the interfacial flow behavior of insoluble phospholipid films involved in human respiration (phospholipid DPPC) and the flow-induced aggregation of soluble protein-based surfactants (insulin). The nonlinear interfacial rheology and important two-way viscous coupling between the surfactants and bulk liquid will be highlighted.

Measuring the interfacial rheology of phospholipid films has garnered significant attention, but the reported surface rheological behavior is often confusing and even contradictory, with the results sensitive to the measurement technique and ad-hoc empirical models explaining behavior. Traditionally, local stresses are measured at small rates of deformation to derive interfacial viscous properties. In contrast, we employ a flow-field based approach where we visualize, measure, and compute the entire flow field to capture material parameters that control the nonlinear interfacial responses. This approach allows access to parameter regimes of interest that are outside the operational range of commercial rheometers. By combining experiments, computations, and theory, I’ve developed a generalized predictive model to describe the flow of phospholipid across the respiratory system during breathing and high-shear events like coughing by adapting bulk (3-D) rheological constitutive relations to interfacial (2-D) rheology. This new theoretical framework can be generalized to other 2-D soft matter systems that are confined to similar hydrodynamic environments.

Utilizing a similar flow-field approach, I will also highlight the role of interfacial stresses and shear in the aggregation and fibril formation mechanism of proteins. The formation of amyloid fibrils is the diagnostic signature of many neurodegenerative diseases and type-II diabetes. However, the role of the dominant and most varying in vivo factors of fluid flow and shear at hydrophobic interfaces in protein aggregation pathways remain poorly understood. Here, I will report the kinetics of fibril formation for human recombinant insulin solutions in an interfacial shearing flows using a cadre of bio-analytical techniques across a wide range of rotation rates. We identify differences in the morphology of the fibril structures formed at the air/fluid interface and in bulk solution at different stages of fibril seeding and growth. An extension of this research will now be performed on the International Space Station (ISS), on a newly developed biophysics platform called the Ring-sheared Drop (RSD).

Bio: Aditya Raghunandan (Adi) is a postdoctoral researcher in the Mechanical, Aerospace & Nuclear Engineering (MANE) department at Rensselaer Polytechnic Institute (RPI). He received is Ph.D. in Mechanical Engineering in May 2018 from RPI, working with Prof. Amir Hirsa. His broad research interests lie at the intersection of experimental fluid mechanics, soft matter biophysics, rheology, and their impacts on human health. His graduate research focused on studying the interfacial hydrodynamics and rheology of biomolecular surfactant films using canonical interfacial flow devices and mathematical modeling. As a postdoctoral researcher, Adi is now working with engineers from NASA to study the biophysics of protein aggregation aboard the International Space Station. He has also had the unique opportunity to lead multiple student teams and conduct proof-of-concept experiments in simulated zero-gravity. Results of his research have been published in journals including Physical Review Letters, Journal of Fluid Mechanics, Physical Review Fluids, Microgravity Science and Technology and have made the cover of Soft Matter.