Lipid-bilayer membranes, which are essential for the organization and function of all cells, are astonishingly complex. In addition to their roles in protection and compartmentalization, membranes are responsible for a variety of other functions, such as signaling, transport, and adhesion, which are executed by membrane proteins. In fact, the cellular membrane is loaded with proteins: Roughly half its mass is comprised of proteins bound to or embedded within the membrane. The physical forces acting between membrane inclusions are essential to their assembly and function, yet understanding how such forces assemble highly ordered structures like “purple membrane” or fold membranes into complex, three-dimensional structures, is challenging.
We aim to develop in vitro experimental systems, consisting of few, well-controlled components, to study the physical forces between membrane inclusions, as well as how these forces give rise to organization of membrane-bound objects. This work is supported by Brandeis' Materials Research Science and Engineering Center.
We have two primary directions within this research area:
Measuring multivalent adhesion. Nature has evolved numerous systems in which adhesion is mediated by multivalent ligand-receptor binding: viruses target their hosts using cooperative binding of weak sugar-protein complexes and neutrophils adhere to the epithelium by . What are the key advantages of having many weakly binding complexes? And how does the net adhesive force depend on the individual molecular attributes, such as their affinity and mobility?
Studying membrane-mediated assembly. How do membrane distortions caused by the adhesion of molecules or small particles induce long-ranged elastic interactions? What new types of architectures can be assembled by combining long-ranged elastic interactions with other short-ranged interactions?
Measuring multivalent adhesion
Our first interest is in building a quantitative understanding of how many weak ligand-receptor pairs conspire to induce specific interactions between small particles and fluid bilayer membranes. Here we use a technique called “total internal reflection microscopy” (TIRM) to measure the interactions between DNA-coated colloidal particles and a DNA-labeled supported lipid bilayer with nanometer precision and kilohertz dynamics. How do? How does?
Studying membrane-mediated assembly
We also seek to explore the wrapping states of free membranes around bound particles which depends on the competition between adhesion and bending. To do so, we have created DNA-functionalized Giant Unilamellar Vesicles (GUVs) whose size and tension we adjust by using various buffers. We characterize how membranes bend to wrap around DNA-grafted colloidal particles upon adhesion. In particular, we explore the role of particle size on membrane bending and on the choice between tension dominated to bending dominated membranes (or vice-versa). Ultimately, we want to characterize how the interplay between adhesion and bending energies affects the GUV’s wrapping states around bound particles.