Increase of temperature results in

Increase of temperature results in greater flexibility of the proteins and an increased tendency for collision, leading to aggregate formation. An increase of the ionic strength may lead to neutralisation of the surface charge on the protein molecules which is responsible for their mutual repulsion, again resulting in aggregation. Charge neutralisation and subsequent aggregation can also occur when the pH of the solution approaches the isoelectric point of the protein. In both cases, molecules in the aggregated state can undergo denaturation with time as a result of subtle changes in their conformation and the aggregation process becomes irreversible.
Two basic pathways have been observed for proteins during denaturation and folding. The simplest is a twostate model. If we refer to the native state as N and the unfolded, denatured state as D, we can write