It is well known that the symmetry of an assembly of identical molecules may differ from the symmetry of a single molecule. However, it is impossible yet to predict based on the structure of a given molecule how an assembly of such molecules will behave and what structure will it form. Clearly it is even more difficult to know how different molecules will self-assemble. It is also not clear how can we change the structure of preassembled molecules. Living systems evolve and function by dynamic self-assembly of a collection of biomolecules. The structures that form are controlled by various molecular parameters including charge, hydrophobicity, size, shape, optical configuration and steric conformations. Understanding the rational behind the manner by which a collection of molecules self-assemble, both at the state of equilibrium and at states that are far-from-equilibrium, and understanding how to manipulate self-assembled structures, will shed light onto their function and help to design therapeutics and biomaterials for biotechnological and biomedical applications such as drug delivery, immunology and tissue engineering.
Our research is focused on the self-assembly of biomacromolecular complexes. We are investigating both the equilibrium structures and dynamic aspects associated with the process of self-assembly, and follow in real-time the association of biomolecules into large and complex structures. Our aim is to reveal the intermolecular forces between the biomolecules, which dictate their assembly dynamics.
Currently, we are investigating lipid bilayers, viruses, microtubules, and Flagellar Filaments. Microtubule form hollow cylindrical structures that are highly dynamic, even when steady-state is attained. The SV40 virus self-assembles into an icosahedral symmetry with a highly robust capsid yet maintains a dynamic internal structure of its genetic material. We are also following the assembly of Hepatitis B virus capsid, a well behaved and tractable model system. Lipid bilayer form flat or curved surfaces with a high level of control and flexibility of molecular design. These systems are enabling us to examine rigorous physical models of intermolecular interactions. The regular tools of structural biology has limited means to approach these structures.
By combining solution X-ray scattering, electron microscopy, osmotic stress, sophisticated analysis tools (developed in our lab), and our gained knowledge in soft matter physics, we are developing new ways to reveal the dynamic structures and intermolecular interactions that govern these involved self-assembled architectures.
Currently, the projects are funded by NIH, BSF, and ISF.