Lipid membranes form the envelope surrounding the interior of biological cells. These membranes exhibit unique mechanical and electrical properties that interact in such a way as to facilitate a wide range of biological processes. The structure of the lipid molecules that constitute these membranes imparts unusual mechanical behavior resembling that of liquid crystals, a phase of matter intermediate between conventional solids and liquids. Another basic feature of plasma membranes is a negatively charged inner layer of lipid molecules. These charged lipids diffuse on the membrane surface in response to physical forces. In turn, charged lipids play a significant role in regulating the functionality of membrane-embedded protein structures. The objective of this project is to formulate and employ mathematical and computational models to investigate electro-mechanical interactions of lipid-protein systems. Insights gained from the project will lead to improved understanding of physical processes occurring at the cellular level. This in turn is expected to enhance understanding of the mechanisms underlying lipid-associated diseases and the efficacy of drug therapies. Thus, the project will promote the progress of fundamental science and advance national priorities in the critical area of healthcare. The project combines expertise in various branches of physics, structural engineering and cellular biology. It will provide advanced training to a diverse group of students and thereby enhance U.S. global competitiveness by contributing to the establishment of a new generation of interdisciplinary scientists and engineers.
This project will provide the mathematical framework to describe the fundamental interactions of charged lipids and proteins in biological membranes. It will culminate in a predictive tool for the simulation of the microscopic electromechanical interactions responsible for a host of cellular functions. Its novel features include the use of continuum theory and molecular dynamics modeling of the coupled interplay between membrane deformation at the lipid-protein interfaces, diffusion of charged lipids and proteins, and the quantification of the role of electric fields on the behavior of the combined system. The derived framework would also assist researchers in the mechanics and material science communities to model complex 2D interfaces.
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.