Electrostatics of Soft Biomolecular Assemblies

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This theoretical project incorporates into Poisson-Boltzmann theory ionic degrees of freedom and applies the extended theoretical formalism to four different biomolecular assemblies. Each assembly highlights a particular degree of freedom and thus exemplifies the crucial importance of intraionic correlations for electrostatic interactions in cellular systems.The first project concerns the lateral distribution of charged lipids in a biomembrane. It addresses the experimentally observed inability of small peptides to laterally sequester monovalent lipids which has currently no satisfactory explanation. The second project models the previously neglected influence of the dipolar moments of zwitterionic lipids on electrostatic membrane-macroion interactions. Theobjective is to explain differences that are observed for cationic and anionic membranes and their interactions with macroions such as DNA. The third project investigates the bridging interaction between macroions mediated by rod-like ions. These ions appear, for example, as DNA condensing agents such as polyamines or cytoskeletal components. The fourth project studies complexes formed from DNA and ionizable cationic polymers. Here, the aim is to model the proton sponge mechanism through which a DNA polyethylenimine complex is believed to escape the endosome.In all four cases, the methodological approach is to incorporate into the variational formalism of mean-field electrostatics ionic degrees of freedom, among them variable polarization, dipolar and higher-order moments, and ionization. Intra-ionic correlation lengths that exceed the Debye length will give rise to a non-local PB equation.The research will improve our ability to understand and design several bio-relevant macro-ionic assemblies, such as membrane-peptide complexes and soft cationic macroion-DNA condensates. Dissemination of the results in national meetings and colloquia will account for the inter-disciplinary character of the work. The project integrates into the Physics Department's new focus on soft condensed matter with emphasis on computational methods and biophysical applications. The educational aspect involves training of two graduate students and the introduction of a new graduate course (Understanding Membranes in Pharmaceutics andPharmacology from a Physical Perspective) shared by the PI.Non-Technical :In this project the techniques of computational physics will be applied to simulate a series of problems related to biomembranes. Biomembranes comprise a significant part of all cells that make up all living matter. The research conducted under this award will further our understanding of these important systems. The research is an example of a revolution occurring in physics departments as the methods of physics research are applied to biological systems. In addition to the importance of the research, of equal importance is the training of a new generation of students in using these techniques on problems of biological interest.