  We extend our previous stochastic cellular automata based model for areal
aggregation of prion proteins on neuronal surfaces. The new anisotropic model
allow us to simulate both strong beta-sheet and weaker attachment bonds between
proteins. Constraining binding directions allows us to generate aggregate
structures with the hexagonal lattice symmetry found in recently observed in
vitro experiments. We argue that these constraints on rules may correspond to
underlying steric constraints on the aggregation process. We find that monomer
dominated growth of the areal aggregate is too slow to account for some
observed doubling time-to-incubation time ratios inferred from data, and so
consider aggregation dominated by relatively stable but non-infectious
oligomeric intermediates. We compare a kinetic theory analysis of oligomeric
aggregation to spatially explicit simulations of the process. We find that with
suitable rules for misfolding of oligomers, possibly due to water exclusion by
the surrounding aggregate, the resulting oligomeric aggregation model maps onto
our previous monomer aggregation model. Therefore it can produce some of the
same attractive features for the description of prion incubation time data. We
propose experiments to test the oligomeric aggregation model.
