By Alan Osborne Updated Mar 24, 2022
Both internal and external regulators play a pivotal role in timing the interval between successive cell divisions—the cell cycle. Cells must divide because, when they become too large, their membrane cannot efficiently transport nutrients and waste products. Every cell is surrounded by a plasma membrane that separates its interior from the external environment.
Cell division is essential but energetically costly and prone to errors. Prior to mitosis, each cell must faithfully replicate its DNA; this genetic blueprint ensures that the two daughter cells inherit all necessary information to function and grow. Built‑in regulatory mechanisms minimize mistakes and guard against uncontrolled proliferation.
Internal regulators are proteins that monitor changes within the cell. For example, a checkpoint protein prevents entry into mitosis until DNA replication is complete. Another internal regulator verifies that replicated chromosomes are properly attached to the spindle apparatus before segregation begins. These safeguards ensure that division proceeds only when the cell is ready.
External regulators are also proteins, but they respond to signals from outside the cell. They can accelerate or slow the cell cycle based on environmental cues. A classic example is a protein that detects molecules on neighboring cells, halting division when cells become overcrowded. This mechanism explains why, in a petri dish, cells grow into a thin monolayer before ceasing proliferation.
The fundamental distinction is that internal regulators react to intracellular stimuli, while external regulators respond to extracellular signals. Without these checks, cell growth would be erratic and dangerous. Disruption of regulatory pathways underlies many diseases, including cancer, where cells ignore density cues and form invasive tumors. External factors such as smoking, radiation, or viral infection can further impair regulatory control.