The formation of amyloid fibrils is a generic characteristic of proteins and peptides and, it is not exclusive to proteins that cause diseases. A large number of proteins aggregate to amyloid fibrils or amyloid-like states under non-biological conditions. During amyloid formation of different proteins, an unfolded or LY2835219 partially unfolded state causes the formation of non-fibrillar aggregation prior to amyloid formation. Amyloid fibril formation consists of a series of stages including soluble oligomer aggregation as a result of nonspecific interactions, protofibrillar structure formation and their assembly to mature fibrils. Insulin prefibrillar aggregations have a low content of beta sheets in comparison with mature amyloid fibrils. The different aggregate forms of proteins are cytotoxic and can disrupt various biochemical processes including cell membrane and normal ion gradient, inactivate other normal, functional proteins and obstruct chaperon proteins, initiate membrane permeabilization, generate reactive oxygen species and dysregulate cytosolic Ca2+, induce apoptotic responses and finally cell death. Cytotoxicity of amyloid aggregation formed by proteins, whether associated with diseases or not, is an inherent phenomenon and correlates with their common structure and not the sequence of amino acids. It has been shown that oligomeric intermediates are more toxic species relative to mature fibril forms. Thus, exploring the processes that are involved in the formation of these intermediates is of significant importance. Insulin is a protein hormone which regulates glucose uptake by binding to insulin-receptors in the surface of cell membrane that result in stimulating of signaling pathway in cell. It has a small structure including two helical chains, which are linked through two disulfide bonds. Insulin amyloid formation is characteristic of localized amyloidosis that is observed in patients with insulin dependent diabetes who frequently receive insulin. The fibrillated forms of insulin lose therapeutic effectiveness and can trigger immune responses as a result of frequent injections. In vitro, insulin has a tendency to undergo fibrillation under conditions that result in partially unfolded intermediates such as high temperature, low pH, high concentration, and incubation with organic solvents. Kinetics of insulin fibrillation is like kinetics of other proteins and includes three stages nucleation, elongation and saturation. The cytotoxicity of insulin fibrillar species has been observed in rat pheochromocytoma PC12 cells and pancreatic b-cells. So, in the present work, we used insulin as a model system for studying amyloid fibrillation. In the aqueous solution containing protein molecules, the changes in protein concentration, pH, temperature and salt ions, which affect protein structural stability and conformation, alter the surface tension of solutions at the air/water interface. The solution surface tension is an important criterion which correlates with protein conformational stability and aggregation. It has been demonstrated that an increase in surface tension of aqueous solution with small molecules results in stabilization of insulin and inhibits its aggregation. The alteration of surface tension by targeted peptides has also different impact on protein aggregation. Thus, surface tension is a feature of protein hydrophobicity at the interface layer of aqueous solution and is used to determine the conformational changes and stability of proteins. In the living cells, morphology has an important role in cellular function especially in specialized cells such as neurons, which is referred to as “function follow form” principle.