Force Is Not Strength: Lessons from Single-Molecule Mechanical Measurements of Protein Dissociation from a Lipid Bilayer with Gavin King

Interactions between polypeptide chains and lipid membranes are central to many biological processes, yet the molecular determinants of peptide partitioning into and dissociation from lipid bilayers remain poorly understood. We investigated these interactions using atomic force microscopy (AFM)-based force spectroscopy combined with molecular dynamics simulations. The lecture will focus on extending force precision into the sub-pN regime and applying the method to a family of short hydrophobic peptides that forms the basis of a widely used hydrophobicity scale. We found that increasing the amino acid chain length raised the dissociation barrier and prolonged membrane residence time while producing little change in the rupture (dissociation) force. In addition, introducing a single hydrophilic residue substantially altered binding stability. Together, these findings show that dissociation kinetics can be more sensitive than rupture force to small changes in peptide sequence and length. I will conclude with reflections on our current work applying ice lithography, an emerging nanofabrication technique that employs solid-phase condensed gases as sacrificial resist, to further improve the precision of biological AFM measurements.

Students are invited to stay after the seminar for an NRT LinQ sponsored roundtable discussion with the speaker. Snacks will be provided. 

This lecture was made possible by the William C. Ferguson Fund.