I am interested in environmental and biochemical applications of colloidal
phenomena. Colloidal and surface forces determine the behavior of systems with high
surface/volume ratios. Although our understanding of these systems is based on assumptions
of "ideal" surfaces, real surfaces are rough and heterogeneous. Recent work
indicates that the spatial distribution of surface heterogeneity has a profound effect on
colloidal systems. My research deals with two very different systems where surface
heterogeneity is important.
Many important industrial materials such as paints, coatings, ceramics, and
pharmaceuticals are produced from suspensions of colloidal particles. These systems have
such high surface/volume ratios that the bulk properties, which are governed by
interactions between particles, are actually determined by the surface properties of the
particles. The projects below focus on understanding these interactions and their effects.
Colloidal interactions in protein systems.
Heterogeneous charge distributions on proteins contribute
to the unique interactions between molecules in solution. By altering the conditions in
solution, we can exploit small differences in the interactions to separate and purify
mixtures of proteins. Such separations are essential in the production and purification of
pharmaceutical materials. We have developed models of protein interactions that account
for the heterogeneous charge distribution on protein molecules and have used the models to
examine the thermodynamic behavior of dilute protein solutions. We plan to perform
additional computer calculations and simulations to extend the model to mixtures of
proteins.
Protein crystal growth.
We are studying the interactions involved in the growth of
protein crystals. In a process known as "rational drug design," knowledge of
molecular structure and function are combined to synthesize highly specific therapeutic
agents. This approach was used to develop protease inhibitors, a class of compounds used
to treat AIDS. The rate-limiting step in the process is obtaining protein crystals for
X-ray diffraction studies. We plan to use our models for heterogeneously charged molecules
to identify likely crystallization conditions, thereby accelerating the discovery of new
pharmaceutical agents. We will also extend the model to investigate the interactions
between molecules in a crystal lattice to determine the reasons why some proteins are
extremely difficult to crystallize.
Charge heterogeneity and colloidal materials processing.
When colloidal particles coagulate, they usually form
relatively loose aggregates. Over time, this loose network of particles can rearrange to
form a more ordered (crystalline) phase, but little is known about this process. Since
colloidal nanocrystals have found applications in drug delivery and chemical sensing, it
is important to know the conditions where colloidal crystals will develop. Each step in
the formation of aggregates is governed by local variations in the surface charge
distribution, so it is important to account for these variations when interpreting
experiments, making theoretical predictions, or optimizing processing conditions. We are
currently carrying out computer simulation studies to investigate and quantify the effect
of chargeheterogeneity on the stability of colloidal suspensions, the mechanical
properties of colloidal aggregates, and the development of nanocrystals. The results of
these studies will be used to optimize the processing of nanocrystals with
"designer" properties.
Selected Publications
"Effects of Thermodynamic Nonideality in Protein Crystal Growth," M.L. Grant,
Journal of Crystal Growth (in press).
"Long-term Studies on Tetragonal Lysozyme Crystals
Grown in Quiescent and Forced Convection Environments," M.L. Grant and D.A. Saville, Journal
of Crystal Growth, 153, 42 (1995).
"Electrostatic Interactions Between a Nonuniformly
Charged Sphere and a Charged Surface," M.L. Grant and D.A. Saville, Journal of
Colloid and Interface Science, 171, 35 (1995).
"Colloidal Interactions in Protein Crystal
Growth," M.L. Grant and D.A. Saville, Journal of Physical Chemistry, 98,
10358 (1994).
