Collaborative Research: GOALI: Nanoparticle analysis of antibody colloidal interactions and their influence on viscoelastic properties of concentrated antibody solutions

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Most of the best-selling drugs today are monoclonal antibodies, which are being used to treat a wide range of human disorders. Antibodies are molecules that interact specifically with objects in the body as part of the natural immune system. One reason for the high cost of drug development is the long and unpredictable process of trying to find the right molecule. Many molecules that are tried do not work. One way in which they fail is that the drug solutions become so thick that they cannot be delivered to the patient. This project aims to develop technologies for rapidly and cheaply determining which drug candidates have this problem as well as how to modify drugs to make them more effective. These findings can potentially lower drug development costs and thereby the cost of new drugs to patients.The viscous nature of concentrated antibody solutions results from pairwise and higher order interactions between antibodies. In this project, these antibody interactions will be measured using a nanoparticle-based technique previously developed by the investigators. By engineering changes to solvent-exposed regions on the antibody surface and measuring the total effective intermolecular interaction, it will be determined how different parts of the antibody surface combine together to give rise to the overall behavior. The viscous response of antibody solutions will also be predicted using antibody interaction measurements as inputs to computer simulations. The investigators will also use computer simulations to determine how antibody interactions cause abnormally high solution viscosities. The combined experimental and computational findings are expected to lead to better methods for predicting how changes in antibody sequence and structure impact viscosity. Therefore, this project holds significant potential to enable the rational design of new antibody molecules with drug-like properties. The project will train undergraduate and graduate students in key aspects of physical science and engineering at scales ranging from molecular to macroscopic. Another key focus of this work is the development of outreach programs to underrepresented minority students.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.