APPLICATION OF SCATTERING MATRIX METHODS IN VIROLOGY

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Applications of scattering matrix methods in virology. Abstract. The goal is to make light scattering a more useful tool in virology, exploiting polarization effects that are hypersensitive to variations in particle structure, but which may be measured only when the scattering particle is as large as a virus. We will attempt to prove the practicality of our method through initial studies of the kinetics of TMV assembly with natural and foreign RNA, and with and without the assembly initiation site. The scattering of polarized light is completely described by a matrix containing sixteen elements, each one a function of scattering angle. Measurement of the distinctive shapes of these sixteen curves tells us all that we will ever know about the sample by means of light scattering. The matrix divides naturally into six 'dipole' elements and ten 'nondipole' elements The nondipole elements were ignored in the early development of light scattering, because they are too small to measure in scattering by small molecules. But in scattering by very large bioaggregates such as viruses they are often not difficult to measure, and can carry important information about the structure and dynamics of the aggregate. The main hindrance to their use has been the lack of instruments to measure them and the lack of theory to interpret such measurements. Work is proposed on both experiment and theory. (1)Proposed experimental work. (a) improvements to our instrument which will allow us to use blue light; (b) continued development of preps for virus samples to make them suitable for scattering experiments; (c) studies on TMV-like synthetic rods of precisely uniform and controllable length, including real-time kinetic studies of rod assembly; (d) investigation of scattering from partially oriented ensembles of viruses, testing theoretical predictions made by ourselves; and (e) basic studies on the Mueller matrix signature of simultaneous absorption and scattering. (2) Proposed theoretical work. (a) continued development of rapid algorithms for predicting the sixteen scattering curves, from a model of the virus and its chromophores; (b) an analysis of scattered intensity fluctuations in terms of the sixteen fundamental curves, laying a theoretical basis for measuring the mechanical elasticity of viruses and other aggregates, as they are perturbed by Brownian forces in the liquid medium.