Self-Assembly of Condensed Biomolecular Phases

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This work is centered on the phase behavior, structure and governing interactions in a general class of biomolecular self-assembled systems, where condensed arrangements of charged biopolymers are formed through their interactions with oppositely charged micro-ions or macro-ions of varying complexity. Intuitively, two like-charged objects in aqueous solution are expected to repel one another. .In the presence of multivalent macro-ions or micro-ions, however, many biopolymers can attract one another and condense into compact ordered states. Examples include DNA condensation by charged histone proteins in chromosome: and the hierarchical organization of the actin cytoskeleton. The origin of this attraction is at present poorly understood. This project aims to delineate the physical mechanisms responsible for these complex molecular organizations. Various forms of counterion correlations have been proposed as possible mechanisms for the observed anomalous attraction. These ideas will be tested for tile first time, along with an investigation of the global biopolymer phase behavior, using a combination of synchrotron x-ray scattering, epifluorescence microscopy, and electron microscopy. These entropically modulated electrostatic interactions will be exploited to develop new self-assembled Systems with a wide range of applications, including drug or gene delivery vehicles, templates for protein crystallization, and biosensors. The multi-disciplinary nature of this work will provide unique educational opportunities for the new kind of hybrid scientists necessary in this emerging field. The students will be prepared for a range of careers in academia, industry, or government %%%This work is directed at the structure and governing interactions of a general class of biomolecular self-assembled materials, where condensed arrangements of charged biological polymers are formed through their interactions with oppositely charged micro-ions or macro-ions of varying complexity. Intuitively, two like-charged objects in aqueous solution are expected to repel one another. In the presence of multivalent macro-ions or micro-ions, however, many biological polymers can attract one another and condense into compact ordered states. Examples include DNA condensation by charged proteins in chromosomes and the hierarchical organization of the actin cytoskeleton. The origin of this attraction has been the recent subject of intense theoretical debate, but no consensus has emerged. Further, there exists no quantitative empirical evidence to discriminate among the many suggested explanations. Using a range of advanced experimental techniques, including synchrotron x-ray scattering, fluorescence microscopy, and electron microscopy, this program aims to delineate the physical mechanisms responsible for the formation of these complex self-assembled biomolecular systems, and to develop new materials based on their novel governing interactions. These material systems have a wide range of applications, including drug or gene delivery systems, templates for protein crystallization, mid biosensors. The multidisciplinary nature of this work will provide unique educational opportunities for the new kind of hybrid scientists required for this emerging field. The students will be prepared for a range of careers in academia, industry, or government.