Extraction, stabilization and crystallization of membrane proteins

Membrane proteins sit inside biological membranes, thin lipid layers that control how cells communicate and exchange molecules. These proteins — channels, transporters, receptors — are essential for life and rely on their surrounding lipids to stay properly folded and active.
Despite their importance (nearly 60% of FDA-approved drugs target them), membrane proteins are hard to study: they are scarce, fragile once removed from the membrane, and prone to aggregation. This is why they still represent less than 1% of all solved protein structures.

At S2CB, we develop chemical tools and membrane mimetics to overcome these challenges. Our work focuses on:

• Engineering next-generation detergents, polymers, and nanodisc-forming systems that recreate key features of the native bilayer.
• Fully characterized them through chemical techniques (NMR, IR, HPLC, SEC)
• Evaluate their colloidal behavior: ability to self-assemble, CMC, size and shape of aggregates

By combining rationale design, synthetic chemistry, biophysics insights we create innovative tools that improve yield, stability, and structural quality — enabling deeper understanding of membrane protein function and accelerating drug discovery.

 

🧰 Our Research : Chemical Tools for Membrane Protein Isolation and Study

At S2CB, we design, synthesize, and evaluate innovative amphiphilic molecules to control each stage of membrane protein handling.

• Extraction – Disrupting lipid bilayers with precision to release target proteins.
• Stabilization – Recreating a protective environment that preserves structure and activity.
• Purification & Structural Analysis – Obtaining homogeneous, functional complexes compatible with advanced biophysical methods.

 

🧪 Our Expertise : Designing Next-Generation Amphiphiles

We develop tailor-made chemical tools to address the specific challenges of membrane protein biochemistry:

✔ Novel detergents
Sugar-based, fluorinated, branched, cyclic or hybrid amphiphiles; low-CMC and HLB-tuned surfactants; additives; detergents enabling native nanodisc formation.

✔ Functionalized amphiphiles
Affinity-tagged molecules, spin-label compatible detergents and additives.

✔ Polymeric tools
SMA-like copolymers and amphiphilic polymers produced via RAFT and PET-RAFT polymerization.

✔ Membrane mimetics
Bicelles, nanodiscs, amphipols, and copolymer–lipid assemblies.

✔ Rational design approaches
Structure–property relationships, HLB engineering, packing parameter optimization, topology–function correlations.

Our tools are tested across diverse membrane protein families — GPCRs, transporters, channels, β-barrels — and integrated into collaborative structural biology pipelines.

 

🎯 Impact

Our research leads to powerful molecular tools that enable:

• higher extraction yields for fragile membrane proteins,
• improved long-term stability and functional activity,
• better crystallization and cryo-EM readiness,
• deeper insights into lipid–protein interactions and membrane organization.