Multiscale Simulations of Droplet-Membrane Mutual Remodelling

点击翻译按钮获取中文摘要

In cellular biology, intracellular phase separation has garnered much attention recently as a means to organise intracellular solutions through the formation of droplet-like sub-compartments. Examples of such droplet compartments include the stress granules and P-bodies.Key to this project is that these droplets interact with membranes, and as a result, the droplets and the membranes can mutually remodel their shapes and morphologies. For example, during autophagy, membrane sheets remodel into double-membrane organelles called autophagosomes. Autophagosomes can selectively isolate cargoes for elimination, including harmful cytosolic droplets. In fact, numerous physiological processes have been identified with similar membrane morphologies, suggesting that these droplet-membrane interactions are a general cellular mechanism.The aim of this interdisciplinary project is to develop the much-needed understanding of these droplet-membrane interactions, and their mutual remodelling during droplet isolation. Here, we will use a multiscale modelling approach. At the molecular level, we will employ molecular dynamics simulations to study the formation of the droplets via a liquid-liquid phase separation mechanism and the affinity between the droplet and membrane. These results will inform a continuum modelling approach based on elasticity theory for studying the droplet and membrane shapes. The theoretical/computational work by the student will also provide an important framework to rationalise and guide ongoing in vitro and in vivo experiments. Our long-term goal is to provide new insights into processes inside cells exploiting this novel physical mechanism based on droplet-membrane interactions.