Abstract
We have used high resolution AFM based dynamic force spectroscopy to investigate peptide-lipid membrane interactions by measuring the detachment (last-rupture) force distribution, P(F), and the corresponding force dependent rupture rate, k(F), for two different peptides and lipid bilayers. The measured quantities, which differed considerably for different peptides, lipid-membranes, AFM tips (prepared under identical conditions), and retraction speeds of the AFM cantilever, could not be described in terms of the standard theory, according to which detachment occurs along a single pathway, corresponding to a diffusive escape process across a free energy barrier. In particular, the prominent retraction speed dependence of k(F) was a clear indication that peptide-lipid membrane dissociation occurs stochastically along several detachment pathways. Thereby, we have formulated a general theoretical approach for describing P(F) and k(F), by assuming that peptide detachment from lipid membranes occurs, with certain probability, along a few dominant diffusive pathways. This new method was validated through a consistent interpretation of the experimental data. Furthermore, we have found that for moderate retraction speeds at intermediate force values, k(F) exhibits catch-bond behavior (i.e. decreasing detachment rate with increasing force). According to the proposed model this behavior is due to the stochastic mixing of individual detachment pathways which do not convert or cross during rupture. To our knowledge, such catch-bond mechanism has not been proposed and demonstrated before for a peptide-lipid interaction.
Highlights
Peptide-lipid interactions are essential for understanding numerous cellular processes and their mechanisms
For peptide-lipid membrane detachment, k(F) depends strongly on the retraction speed and has non-monotonic behavior in F, implying that for such systems multiple detachment pathways are in play
We demonstrate the viability of the proposed model by applying it to atomic force microscopy (AFM) retraction experiments, performed under different experimental conditions, that involve two different peptides and two species of lipid bilayers
Summary
Peptide-lipid interactions are essential for understanding numerous cellular processes and their mechanisms. The values of the model parameters are determined by fitting the theoretical prediction to the experimental P(F) While such an approach is applicable to other force-induced molecular transitions (e.g., unfolding of proteins[9,10,11,12,13,14], unzipping of nucleic acid hairpins[15,16], ligand-receptor dissociation[17,18], etc.), our experimental results indicate that the single detachment pathway model fails for peptide-lipid membrane systems, most likely due to their complexity. In general, the probability that detachment follows a certain pathway should change by modifying the experimental conditions
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