Computational Molecular Modeling and Experimental Biophysics
Perlmutter et al. 2009
Our interest is in the structural and dynamic properties of large-scale, self-assembled macromolecular complexes, such as biological membranes. As the fundamental component of sub-cellular organization, the membrane impacts nearly every aspect of cell biology: from cell growth and movement to signal transduction and intracellular transport of proteins. The membrane is composed of a surprisingly diverse array of lipid molecules that have the ability to self-assemble into a liquid-crystalline bilayer. The lipids provide more than a mere structural scaffold for the transmembrane protein machinery. By modulating the lipid composition of the bilayer, cells can fine-tune the protein environment and significantly affect protein function. We are interested in the specific, single-molecule chemical interactions within the membrane, and further, how the collective material properties of membranes, such as thickness and compressibility, result from the sum of these individual components. In order to engineer biomedical technologies that act at the membrane, it is important to understand how and in what circumstances the cell exploits these different levels of organization. Biophysical approaches to the study of membrane structure are especially fruitful in establishing the underlying principles of local and global bilayer organization. Computer simulations have traditionally been suited for chemical descriptions on the local level. Meanwhile, experiments have addressed the global level. Now, for the first time, advances in computer power and experimental techniques promise to transcend these limitations. It is our goal to combine computational simulations and experimentation in order to draw meaningful connections between the two levels.