Speed limits of protein assembly with reversible membrane localization

Area of Science:

• Biophysics
• Cell Biology
• Biochemistry

Background:

• Protein assembly is crucial for cellular functions.
• Many protein interactions occur on 2D membrane surfaces, not just in 3D solution.
• Reduced dimensionality on membranes can alter reaction kinetics.

Purpose of the Study:

• To quantify how proteins use reduced dimensionality on membranes to accelerate complex formation.
• To derive a single expression for the timescale of multi-step protein assembly on membranes.
• To understand how membrane localization affects protein interaction rates.

Main Methods:

• Derivation of a theoretical model for protein assembly timescales.
• Analysis of a complex reaction network involving protein dimerization and lipid binding.
• Identification of rate-limiting pathways to approximate mean first passage time.
• Kinetic and particle-based reaction-diffusion simulations for validation.

Main Results:

• Proteins accelerate dimer formation on membranes due to increased effective concentration and collision frequency.
• The 'sticking rate' (effective adsorption coefficient) is central to controlling assembly timescales.
• Membrane geometry and diffusion can reduce membrane localization rates.
• Assembly speeds can shift by orders of magnitude upon membrane localization.

Conclusions:

• Membrane-bound protein assembly is significantly faster than in 3D solution.
• The theoretical framework provides insights into controlling protein assembly dynamics.
• Understanding membrane-mediated assembly is critical for cellular mechanisms.