Monday, June 4, 2018

3:00pm - 4:00pm

Elasticity as the basis of allosteric interactions in DNA and membranes

AbstractIn mechanics the forces of interaction between defects in an elastic solid are well understood. Just as defects produce local elastic fields in a solid, proteins binding to DNA also deform it locally. Since DNA behaves like an elastic rod at scales of a few tens of nanometers, we expect that if two proteins bind to DNA separated by a distance r then their deformation fields will overlap and lead to an interaction energy that depends on r. This problem has not been theoretically addressed so far, but there is experimental evidence of the interaction.

For example, gene expression, which depends on RNA polymerase binding affinity to DNA, is a function of the proximity of LacR and RNA polymerase. These effects are called allosteric interactions on DNA. In this talk we will use a birod model of DNA to study how proteins deform it locally, and how this leads to allosteric interactions between them.

Similar elastic deformations caused by proteins binding to lipid bilayers also result in allosteric interactions that are responsible for cellular processes, such as, endo- and exo-cytosis required for transport of materials into and out of cells. Often, allostery also involves entropic forces between the proteins that are the result of fluctuations caused by Brownian motion of the elastic media (DNA or lipid membrane) separating them. We will briefly discuss how such entropic interactions between proteins bound to lipid membranes can be described quantitatively within a semi-analytic computational model.

BiographyPrashant Purohit is currently Associate Professor of Mechanical Engineering and Applied Mechanics at the University of Pennsylvania. He got his PhD at Caltech in 2002. His interests are in problems at the interface of mechanics, physics and biology. He has worked on mechanics of DNA, mechanics of blood clots and mechanics of lipid membranes. The interplay of solid mechanics and Brownian motion in these and other problems is of particular interest to him.