This award supports theoretical studies and education at the intersection between condensed matter physics, computational materials science, and membrane biophysics. The projects focus on spatial organization, regulation, and non-equilibrium dynamics of heterogeneous, multicomponent lipid bilayer membranes. Lipid membranes are ubiquitous in mammalian cells, and facilitate the interaction between a cell and its surroundings. Furthermore, lipid membranes are employed in important biomedical applications, such as vehicles for targeted drug delivery. Notably, membrane "microstructure" might arise, for example, from local lipid and protein compositions, and directly controls the mechanical, physical, and biochemical properties of the system.
The PI aims to develop and employ effective, coarse-grained Ginzburg-Landau models for materials behavior across several length scales. These continuum and hybrid particle-continuum models will be employed to address several key questions, including: (1) What are the roles of membrane and exterior solvent hydrodynamics on lipid microdomain formation kinetics? (2) How do the lipid microdomains associate/aggregate? How important are protein-lipid interactions in microdomain aggregation? (3) How are spatio-temporal correlations in the underlying lipid composition fields reflected in reporter particle correlations? Can we devise methods, which facilitate the quantification of sub-micron lipid microdomain structure and correlations from experimental data? (4) What are the effects of spontaneous or induced membrane curvature on lipid raft formation and stability? (5) How are the lipid compositions coupled across the two leaflets? How does this coupling affect lipid microdomain formation and stability?
In the short term, these studies will lead to a better understanding of nonlinear pattern formation and self-organization processes on molecular and mesoscopic scales in biological systems and biomaterials. In the long term, these research and educational activities will (1) contribute to the training of the next generation of scientists at the intersection between condensed matter physics, materials science, and biology, and (2) pave the way for a more fundamental understanding of the role of compositional lipid domains in cellular signaling and trafficking, with potential impact in biophysics, cellular biology, biomaterials, and medicine.
NONTECHNICAL SUMMARY
This award supports theoretical studies and education at the intersection between condensed matter physics, computational materials science, and membrane biophysics. Lipid bilayer membranes are ubiquitous in mammalian cells, and facilitate the interaction between a cell and its surroundings. Furthermore, lipid membranes are employed in important biomedical applications, such as vehicles for targeted drug delivery. Like more traditional materials, such as metals and alloys, the structure of a membrane on length scales longer than the distance between atoms and molecules, but still less than the size of cells, directly controls the mechanical, physical, and biochemical properties of the membrane. The PI will study this microstructure of lipid membranes. He will develop models that are accessible to modern computers and can capture the effects of membrane microstructure in both synthetic and natural lipid bilayer membranes.
The PI aims to advance our fundamental understanding of evolving microstructures in live cells and biomaterials. This will contribute to a better understanding of how molecules and membranes organize themselves in biological systems and materials. In the long term, these research and educational activities will (1) contribute to the training of the next generation of scientists at the intersection between condensed matter physics, materials science, and biology, and (2) pave the way for a more fundamental understanding of the role of lipid microstructure in cellular function with potential impact in biophysics, cellular biology, biomaterials, and medicine.
Multicomponent lipid bilayer membranes comprise a class of soft materials with intriguing physical, chemical, mechanical, and biological properties. They self-assemble spontaneously in an aqueous solvent, and form effectively two-dimensional surfaces embedded within the three-dimensional solvent. They are also ubiquitous in mammalian cells where, together with proteins, they facilitate the interaction of cells with their surroundings. The lipid membrane may be compositionally homogeneous or heterogeneous, and structurally (and thus mechanically) either solid-like or liquid, and even display co-existence between solid and liquid phases or multiple liquid phases with distinct lipid compositions. In this project, our work has focused on developing a quantitative understanding of synthetic multicomponent lipid bilayer membranes, especially their phase transformation behavior and compositional domain formation dynamics. Experimentally, it has been observed that when both leaflets contain domains, they are often found in perfect spatial registry. This indicates that a significant thermodynamic coupling, whose physical mechanisms are still debated, exists between the two leaflets. Now, while the effects of this thermodynamic coupling have been theoretically investigated with regard to equilibrium behavior of membranes, its effects on the compositional domain dynamics have received much less attention. To rectify this, starting from a coarse-grained continuum approach, we have derived the general equations that describe the dynamics of compositional domains within planar symmetric or asymmetric lipid bilayer membranes. The general equations were then employed to develop analytical solutions for the dynamics of the recurrence of registration. The intellectual merit of this work is the development of analytical closed-form solutions that quantitatively describe the nonlinear dynamics of compositional lipid domains. Importantly, experimentally measuring these dynamics would enable one to determine the strength of the thermodynamic coupling between the leaflets, which has remained elusive to date. From a broader impact perspective, a better understanding of the effects of the thermodynamic coupling in synthetic membranes will provide critical insights into the behavior of membrane domains in living systems.
