Practice question

Actin assembly exhibits sigmoidal kinetics reflecting cooperative nucleation mechanism. Lag phase corresponds to nucleation where monomers collide forming unstable dimer with Kd micromolar and trimer tetramer nucleus, high free energy barrier due to entropy loss and weak contacts, hence extremely slow without nucleators. Over minutes trimer accumulates reaching critical nucleus size three to four subunits, providing template for rapid elongation phase where ATP G actin adds efficiently at barbed end with near diffusion limited rate, elongating filament linearly until monomer pool depleted to critical concentration. Eventually steady state reached where on rate equals off rate at both ends, total polymer mass constant while individual subunits treadmill hydrolyzing ATP, known as steady state treadmilling. This order nucleation elongation steady state parallels crystallization, microtubule assembly and amyloid formation. Alternative orders reversing steps violate thermodynamic principle that stable nucleus must form before rapid growth. Pharmacological inhibitors target stages: latrunculin sequesters monomer preventing nucleation, cytochalasin D caps barbed end blocking elongation.