Computational Investigations of Compositional Heterogeneities in Lipid Membranes

University Of Memphis, Memphis TN

Investigators

Abstract

TECHNICAL ABSTRACT: This award supports theoretical research and education in the study of nanoscale heterogeneities in biological membranes, so called ''rafts''. Research on these lateral heterogeneities in biomembranes is motivated by a need to know their physiological and structural functions. The is extensive research indicating that mammalian cells exhibit compositional heterogeneities in the form of small domains, called rafts, with diameter ranging between 50 and 200 nm. Lipid rafts are believed to be highly dynamic, rich in sphingolipids, which are mainly saturated lipids, and cholesterol. Lipid rafts are also believed to play a role in a variety of physiological functions including protein trafficking, lipid sorting, signal transduction, and endocytosis. There are striking questions raised when studying living biological systems in comparison to synthetic membrane. Numerous experiments on synthetic lipid membranes, demonstrated the existence of domains, thus supporting the raft model in biomembranes. However, lipid rafts in biomembranes, which are nanoscale in size, are orders of magnitude smaller than the lipid domains in synthetic membranes. The present research investigates raft formation and dynamics of membrane heterogeneities through systematic and large scale mesoscale numerical simulations. Computer simulations allow the study of phase behavior of multicomponent membranes and investigate possible mechanisms leading to the stability of nanoscale lipid rafts in biomembranes. Using coarse-grained molecular dynamics (CGMD) simulations of a recently developed model, the PI will investigate the phase behavior of ternary lipid mixtures composed of a saturated lipid, an unsaturated lipid and cholesterol, with a particular focus on the two-phase liquid-liquid coexistence, which is relevant to the lipid rafts in biomembranes. A more coarse-grained model based on soft-core interactions will be developed for self assembled amphiphiles and will be used to investigate three-component lipid membranes in the two-phase liquid-liquid coexistence. The model will be used in conjunction with a hybrid approach combining dissipative particle dynamics (DPD) with semi-grand canonical Monte Carlo technique. Beyond the basic research, the award has educational implications and potential broader impact in other areas. Due to its multidisciplinary nature, the research will have a broad impact on both the physical and life sciences. Graduate and undergraduate students are involved in this research. The computational nature of this proposed research makes it particularly accessible to undergraduate students. This research will also benefit the new Computational Physics Concentration at the University of Memphis. The research will be integrated with the current educational agenda of the University of Memphis which has a significant minority student population. The senior undergraduate biophysics course and the graduate computational course at the University of Memphis benefit from this program by the proximity of an active research program which can relate the character of research activities in this area. The PI is also teaming up with other faculty members at the physics department to create a high school physics internship program in which a number of students will be selected every year from the Memphis area high schools and will be involved in research experience projects. NONTECHNICAL ABSTRACT: This award supports theoretical research and education in the study of molecular clustering in biological membranes, so called ''rafts''. Research on these molecular groupings in biomembranes is motivated by a need to know their physiological and structural functions. The is extensive research indicating that all animal cells form these small domains, called rafts, with small diameter of around 1/100th the size of the cell. Lipid rafts are believed to be highly dynamic and mainly saturated lipids, and cholesterol. Lipid rafts are also believed to play a role in a variety of physiological functions, including transfer of materials into and out of a cell. There are striking questions raised when studying living biological systems in comparison to synthetic membrane. Numerous experiments on synthetic lipid membranes, demonstrated the existence of domains, thus supporting the raft model in biomembranes. However, lipid rafts in biomembranes are a hundred times smaller than the lipid domains in synthetic membranes. This is only one aspect of rafts that is investigated in this research. The present research investigates raft formation and dynamics of membrane composition through systematic and large scale numerical simulations. Computer simulations allow the study of membrane composition and investigate possible mechanisms leading to the stability of lipid rafts. Beyond the basic research, the award has educational implications and potential broader impact in other areas. Due to its multidisciplinary nature, the research will have a broad impact on both the physical and life sciences. Graduate and undergraduate students are involved in this research. The computational nature of this proposed research makes it particularly accessible to undergraduate students. This research will also benefit the new Computational Physics Concentration at the University of Memphis. The research will be integrated with the current educational agenda of the University of Memphis which has a significant minority student population. The senior undergraduate biophysics course and the graduate computational course at the University of Memphis benefit from this program by the proximity of an active research program which can relate the character of research activities in this area. The PI is also teaming up with other faculty members at the physics department to create a high school physics internship program in which a number of students will be selected every year from the Memphis area high schools and will be involved in research experience projects.