Protein molecules are the primary solid matter in muscle fiber. In their natural state, protein molecules are typically coil-shaped. They exist as independent units because their spiraled structure hinders their binding with each other. When cooked, however, the protein molecules uncoil and become denatured, allowing them to bind easily with each other and form a mass of joined protein molecules. Overcooking toughens meat because the compacting-joined proteins squeeze out water and shrink muscle fibers. The more the meat is cooked, the tighter the meat mass becomes.

With dry-heat cooking methods (including roasting and grilling), shrinkage and water loss are minimal at the rare state (130°F), noticeable at medium-rare (135° to 140°F), very noticeable at medium (145° to 150°F), pronounced at medium-well-done (155°F), and devastating at well-done (160°F).

Braising and other moist-heat methods are more forgiving because the cooking liquid and steam are trapped in the pan. Still, boiling and even simmering will eventually shrink and toughen meat. It is best to braise meat in a sub-simmering liquid. The gain in tenderness and succulence more than outweighs the extra cooking time.