Biologically, calluses are formed by the accumulation of terminally differentiated keratinocytes in the outermost layer of skin. Though the cells of calluses are dead, they are quite resistant to mechanical and chemical damage due to extensive networks of cross-linked proteins and hydrophobic keratin intermediate filaments containing many disulfide bonds. It is the natural reaction of the palmar or plantar skin. Too much friction occurring too fast for the skin to develop a protective callus will cause a blister or abrasion instead.