Force transduction and lipid binding in MscL: a continuum-molecular approach

Area of Science:

• Biophysics
• Molecular Biology
• Structural Biology

Background:

• Mechanosensitive channel MscL is a key model for mechanotransduction.
• MscL gating is known to depend on protein-protein and lipid-protein interactions.
• A gap exists between chemical details and mechanical models of MscL gating.

Purpose of the Study:

• Investigate the MscL bilayer-protein interface.
• Connect chemical interactions with mechanical gating models.
• Quantify membrane tension effects on MscL.

Main Methods:

• Molecular dynamics simulations.
• Combined continuum-molecular modeling.
• Analysis of force distribution and lipid-protein interactions.

Main Results:

• Membrane tension induces asymmetric forces on MscL, pulling it outward.
• Hydrogen bonds between lipid headgroups and MscL lysine residues are critical.
• These interactions provide strong bilayer anchoring (10-13 kT per lipid).

Conclusions:

• A simple motif confers strong MscL anchoring to the lipid bilayer.
• This motif is conserved in other mechanosensitive channels and proteins like rhodopsin.
• Understanding these interactions advances mechanical models of channel gating.