Overview
Single molecule biophysics lies at the confluence of molecular medicine and nanotechnology. The Center uses nanotechnology to study physical processes on which life is based using the simplest model systems — those that exist on the level of a single molecule or several molecules. By doing this, researchers plan to gain a better understanding of gene regulation, molecular signaling and molecular transport in cells that will lead to improved biosensors and other new technologies.
The Center for Single Molecule Biophysics seeks to better understand the physical basis of life by studying the individual molecules that comprise living cells. Researchers at the Center are using scanning probe methods to measure and manipulate individual molecules. Our premise is that single molecules are simple enough to be molded accurately with computer simulations, yet complex enough to reflect the variations that are important to their function.
The Center is also dedicated to advancing the latest techniques for research on the single molecule scale and to translating discoveries into new tools and new applications that are relevant to promoting health and combating disease. With a clearer understanding of the individual components that comprise integrated living systems, researchers are better able to grasp the many complex interactions between gene products (molecules) that cause disease. By learning from nature’s repertoire of experiments on its own ”nanomachines” researchers at the Center are figuring out how to craft components for machinery of undreamt-of complexity and sophistication.
Our research program is inherently interdisciplinary. The tools are in the domain of engineering and chemistry: nanostructures that connect to molecules and instruments that manipulate and measure at the single molecule level. The interactions and modeling come from physics: understanding the quantum phenomena that dominate interactions on this length scale and building simple models of the complex many-particle phenomena. The systems come from biology: molecules involved in gene expression (signaling and the control of processes in living cells). Finally, the building of molecular model systems and the controlled assembly of nanostructures is dependent upon chemistry, biochemistry and materials chemistry).
The recent evolution in nanotechnology has given us new tools with which researchers can imagine measure, manipulate and modify individual molecules, one at a time. Previous probes of biological molecules, such as X-ray crystallography, inferred their properties by averaging billions of molecules. However, single molecule studies now show that, outside the confines of a crystal, proteins fluctuate through a series of very different structures. Therefore, the crystal structures are often not only inappropriate, but they fail to capture the set of states that the protein uses to do its job.
For example, adhesion proteins must adopt one structure when a cell rests and another (non-sticky) structure when the cell moves. But molecules are in a state of constant fluctuation, with, on average, more of them in the ‘sticky’ state when the cell rests, changing to more in the ‘non-sticky’ state when the cells move. The only way to capture the structural changes that drive the process is to study just one molecule as it jumps between the two states. Thus, single molecule methods are often the only way to follow the changes in structure that rival the fundamental processes of life.
