Marie Adams and Seth Fraden
The Martin Fisher School of Physics
Brandeis University, Waltham, MA
02254
September 10, 1997
Aqueous suspensions of mixtures of the rodlike virus Tobacco Mosaic Virus (TMV) with globular macromolecules such as polyethylene oxide (PEO) or
Bovine Serum Albumin (BSA) phase separate and exhibit rich and strikingly
similar phase behavior. Isotropic, nematic,
lamellar, and crystalline phases are observed as a function of the
concentration of the constituents and ionic strength.
The observed phase behavior is considered to arise from attractions between the two particles induced by the presence of BSA or PEO. For the TMV/BSA mixtures the BSA adsorbs to the TMV and bridging of the BSA between TMV produces the attractions. For TMV/PEO mixtures, attractions are entropically driven via
excluded volume effects known alternatively as the ``depletion interaction'' or ``macromolecular crowding''.
Keywords: depletion,
macromolecular crowding, phase separation, protein crystallization, osmotic
pressure, polymer, liquid crystal.
Dedication
Don Caspar first introduced me (SF) to the fascinating properties of suspensions of Tobacco Mosaic Virus (TMV) in 1980, and I have been studying their liquid crystalline and colloidal properties ever since. Although Prof. Caspar is principally known as a structural biologist, and for his contributions to the elucidation of intramolecular structure, he has had a long interest in interparticle structure and collective organization. The goal of the work presented here is to understand the physical basis of polymer induced crystallization of proteins, a problem of great importance to x-ray crystallography, and in understanding the compartmentalization of DNA and other filamentous molecules in cytoplasm. Not surprisingly, Prof. Caspar has worked on this problem in the past, and a poster containing several of the results presented below hung on the walls of his lab at Brandeis for many years. And not uncharacteristically, Prof. Caspar's work has gone unpublished, perhaps because all the questions posed by the observations were not answered well enough for Don's standards. Our work presented here is far from complete. The problem of polymer induced phase separation has been studied independently by physicists, chemists, and biologists. Often the work from one discipline is unknown to the others. It is the objective of this paper to study experimentally this problem using well characterized, model systems and analyze the observations within the framework of theories known as ``depletion interaction'' or ``macromolecular crowding''.