Proteins cover a range of fundamental functions in the human body: i) the enzymes and hormones are proteins; ii) proteins can carry other biomolecules within the cellular environment.
Proteins can aggregate after they folded in the native state --- through the formation of chemical bonds or self-assembling --- or via unfolded intermediate conformations and their propensity to aggregate is related to a series of factors, like the flexibility of the protein structure or the sub-cellular volume where the protein resides.
Inappropriate protein aggregation represents a crucial issue in biology and medicine, as it is associated with a growing number of diseases such as Alzheimer's and Parkinson's disease.
In order to guarantee the correct biological functions, proteins have evolved to have a low enough propensity to aggregate within a range of protein expression required for their biological activity, but with no margin to respond to external factors increasing/decreasing their expression/solubility. Indeed, protein aggregation is mostly unavoidable when proteins are expressed at concentrations higher than the natural ones.
We present a computational study on the folding and aggregation of proteins in an aqueous environment, as a function of its concentration.  We show how the increase of the concentration of individual protein species can induce a partial unfolding of the native conformation without the occurrence of aggregates. A further increment of the protein concentration results in the complete loss of the folded structures and induces the formation of protein aggregates.

The main conclusion of this work is that proteins tend to fold uninfluenced by the presence of other proteins in the solution provided that their concentration is below their specific unfolding concentration. Our simulations predict an unexpected and not previously observed role of the water in inducing unfolding that we then observe be a precursor of the aggregation. We believe that such prediction should be testable first in more detailed protein models and supports the need for new intriguing experiments.