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#critical concentration

3 public questions tagged with this topic.

Cytoskeleton

In microtubule assembly, what happens when the αβ-tubulin concentration is below the critical concentration?

Polymerization equilibrium of cytoskeletal filaments obeys critical concentration concept derived from actin and tubulin thermodynamics studies of reversible polymers. Binding constant for addition at plus end determined by on rate times free dimer concentration minus off rate dissociation constant. Critical concentration Cc equals off rate over on rate threshold where net growth zero and polymer mass constant. Cellular tubulin concentration about 10 micromolar generally above Cc for plus end promoting growth but may be near Cc for minus. When alpha beta tubulin pool diluted experimentally or sequestered by stathmin effective concentration falls below Cc net loss dominates filaments shrink GTP cap lost catastrophe initiated. Conversely increase above Cc favors nucleation and elongation increasing polymer mass. Unlike covalent polymers microtubules reversible so below Cc no new growth occurs and existing polymers depolymerize to restore pool to equilibrium. In vivo local tubulin gradients regulated by expression autoregulation and sequestration guide where microtubules assemble especially during mitosis where local concentration high near chromatin favoring nucleation.

Ref: Alberts et al., Molecular Biology of the Cell, Chapter 14 – Critical concentration below Cc causes depolymerization.

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Cytoskeleton

What happens when the G-actin concentration is lower than Cc at both ends?

Filament mass reflects equilibrium between monomer pool and polymers determined by two Cc values. Plus end higher affinity due to ATP cap and hydrophobic pocket, minus end lower affinity bearing ADP actin. When total free G actin concentration falls below Cc for both ends, for instance after dilution into low ionic buffer, sequestration by thymosin beta4 or latrunculin A, or after activation of cofilin increasing off rate, association cannot compensate dissociation. Consequently subunits dissociate from both termini, filament shortens from both directions and ultimately disappears. This explains experimental observation where lowering monomer below 0.1 micromolar triggers rapid disassembly throughout cytoplasm, confirmed by loss of phalloidin staining. If monomer concentration lies between 0.1 and 0.8 micromolar, plus end still grows while minus shrinks, creating treadmilling without net change. Concentrations above 0.8 drive elongation at both ends. Filament stability without growth demands accessory proteins like phalloidin or capping proteins preventing subunit exchange, not merely low monomer levels alone.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 16: Actin Critical Concentration and Dynamics.

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Cytoskeleton

The critical concentration (Cc) of actin filaments is defined as the concentration at which:

Assembly of G actin into F actin follows reversible nucleation condensation kinetics characterized by critical concentration. Defined as monomer concentration at which rate of subunit addition equals rate of loss at filament ends, Cc reflects equilibrium constant Kd equal to k off divided by k on. Experimental determination uses pyrene fluorescence plateau where increasing total actin beyond Cc goes into polymer, free monomer stays constant. Because barbed plus end and pointed minus end have distinct kinetic constants due to ATP versus ADP actin states, each end possesses its own Cc approximately 0.1 micromolar for barbed and 0.8 micromolar for pointed under physiological 50 millimolar KCl 2 millimolar MgCl2. Between these values treadmilling operates, barbed elongates while pointed shrinks, net polymer constant. Complete depolymerization requires dropping below both Cc values or adding sequestering drugs like latrunculin. Branch angle 70 degrees relates to Arp2/3 geometry not Cc, and ATP hydrolysis rate is consequence not definition. Understanding Cc enables prediction of growth versus shrinkage and design of polymerization assays.

Ref: Pollard and Earnshaw, Cell Biology, Chapter 12: Actin Polymerization and Critical Concentration.

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