Wet Electrostatics and Biomolecular Self-Assembly

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

In recent years, much progress has been made in understanding the behavior of charged polymers with a single sign of charge (such as DNA), which exhibit counterintuitive behavior such as like-charge attraction. The present project aims to extend this understanding to polymers with both positive and negative charges, which comprise a general class of charged polymers that includes most proteins. Inelastic synchrotron x-ray scattering will be employed to study the mobile ions that mediate interactions between these polymers. Experiments will also concentrate on archetypal interactions between simple geometric objects, such as like-charged rods and sheets (ex. DNA and membranes), or oppositely charged rods and spheres (ex. proteins of different shapes) in the presence of salts with different valences. In particular, molecular biology techniques will be used to engineer protein mutants with charges and sizes that can be independently varied for these studies. This work may lead to new therapeutic strategies for cystic fibrosis, where negatively charged polymers such as F-actin and DNA bind to and inactivate net positively charged antibiotic proteins. An understanding of these effects may also lead to improved methods of water purification processes. The multi-disciplinary nature of the proposed work provides ample educational opportunities for the new kind of hybrid scientists necessary in this emerging multidisciplinary field. In recent years, much progress has been made in understanding the behavior of charged polymers with a single sign of charge, which exhibit counterintuitive behavior such as like-charge attraction. The present project aims to extend this understanding to polymers with large numbers of both positive and negative charges, which comprise a general class of charged polymers that includes most proteins. Experiments will concentrate on archetypal examples of interactions between simple geometric objects, such as like-charged rods and sheets (ex. DNA and membranes), or oppositely-charged rods and spheres (ex. proteins of different shapes) in the presence of salts. In particular, state-of-the-art molecular biology techniques will be used to engineer protein mutants with well-defined charges and sizes for these studies. This work may lead to new therapeutic strategies for cystic fibrosis, where negatively charged polymers such as F-actin and DNA bind to and inactivate net positively charged antibiotic proteins, and thereby contribute to long-term infections. An understanding of these electrostatic effects will also potentially lead to improved methods of water purification processes. The multi-disciplinary nature of the proposed work will provide ample educational opportunities for the new kind of hybrid scientists necessary in this emerging multidisciplinary field.