The role of cortical linkers and the glycocalyx in outward budding: insights from biophysical modeling

Dr. Padmini Rangamani, University of California, San Diego
- | DRL 3W2 and via Zoom

Abstract: Curvature generation in the plasma membrane is critical for cellular function. Many cells in the animal body release extracellular vesicles from their cell surface under normal conditions and exposure to tress. Microparticles are a type of extracellular vesicle that bud directly from the plasma membrane. From a biophysical standpoint, the formation of microparticles can be characterized by three main driving forces: changes to membrane composition and accompanying changes to spontaneous curvature due to phosphatidylserine flipping, loss of membrane-cortex attachment by breaking the adhesive bonds, and pressure driven bleb growth. In this work, we develop a combined model of these three factors and systematically investigate the role of linker adhesion, external loading such as pressure and force, and dynamics of the change of lipid composition in the formation of MPs. Specifically, we focus on the following questions: How do pressure or local forces interact with linker binding to lead to outward bending? What is role played by the kinetics of phosphatidylserine flipping? How does the glycocalyx aid or hinder outward budding? To answer these questions, we develop mechanical models and study how these different factors contribute to membrane bending. Our model predicts that linker binding is a key determinant of MP formation. High linker binding can override other mechanisms of membrane deformation including PS-induced spontaneous curvature and pressure-driven blebbing. We also show that the properties of the glycocalyx including chain length and density can affect outward budding. These findings play a critical role in integrating myriad experimental observations in the literature and providing a unifying mechanical framework for outward budding of the membrane.