Consequences of Asymmetric Environment on the Mechanics of Lipid Bilayer

Lipid membranes are selective barriers that encapsulate cellular components and define the identity of organelles. A fundamental feature of membranes is an asymmetric distribution of lipids and proteins across them. While a basic level of asymmetry is maintained at all times, local and transient increase in asymmetry is achieved to execute drastic morphological changes in the structure of the organelles and the plasma membrane. In this study, we computationally investigate a few such biological processes. First, we model the squeezing of mitochondria and show that asymmetrically distributed proteins and conical lipids can work synergistically to trigger buckling instabilities in order to generate extreme constrictions. Our work provides the physical explanation of the role of lipids in mitochondrial fission for the first time. Second, we model the formation of vesicles induced by asymmetrically distributed proteins during cellular transport. Our study reveals that the energetic cost of remodeling the membrane is highly sensitive to not only the tension in the membrane but also to the instantaneous geometry of the membrane during the shape evolution. Third, we model the adhesion of vesicles to planar substrates induced by asymmetric distribution of proteins across the membrane. Our work furnishes a novel universal relationship for the estimation of adhesion energy of the proteins from the shape of the adhered vesicle. Lastly, we experimentally investigate the role of charge asymmetry on membrane protein interaction. Our results suggest that the charge asymmetry is critical in regulating the level of protein insertion in the membrane which could potentially play a significant role in executing programmed cell death. Overall, our work provides new quantitative insights that could be valuable in understanding the remodeling of asymmetric membranes during other vital cellular processes.