Understanding the dynamics of biological membranes, when they interact with various structurally different molecules, sets the basis for understanding how this interaction is related to many cellular processes including those related to severe diseases. Small cationic peptides show a broad-spectrum of activities on both eukaryotic and prokaryotic cells. Due to their versatile chemical structures, it has been shown that they recognize biological membranes and interact with these in many different ways.
In order to gain insight into the membrane lipid dynamics, a number of experimental techniques can be used, depending on time- and length-scale, e.g. fluorescence spectroscopy, NMR and Quasi Elastic Neutron scattering (QENS). QENS offers the ability to access processes in the ps to ns time range and on a nanometer length scale, in contrast to the other two techniques, which offer no specific selectivity of length scale.
In the present project, we will investigate the change in lipid dynamics when incorporating two classes of molecules into model lipid membranes, both exerting mechanical stress on the membrane: (i) simple alcohols and (ii) antimicrobial peptides . (i) Alcohols are incorporated in the membrane which results in a thinning of the membrane for shorter chain alcohols while longer chain alcohols lead to an increasing thickness of the membrane. The presence of chains with a mismatch in hydrophobic length and the resulting creation of free volume are also expected to influence the dynamics of the lipid matrix. These effects have important implications, for example regarding exploration of the anesthetic effect, and the adaption of membranes for micro-organisms growing in adverse conditions. Likewise, antimicrobial peptides interact with the lipid membrane and increase membrane permeability, however it is unclear to which extent stable pores and holes are formed. Accordingly, it is to be expected that information on changes in the membrane lipid dynamics can shed light on peptide-membrane interactions. The change of the local and collective lipid dynamics will be investigated using a combination of neutron spectroscopic methods, i.e. time-of-flight quasielastic neutron scattering (probing motions in the time domain of 0.01-0.1 ns), neutron backscattering (0.1-5 ns) and neutron spin-echo spectroscopy (time domain 0.1-400 ns). Complementary structural studies will be carried out using small-angle neutron and x-ray scattering and neutron and x-ray diffraction.
The combination of these methods enables to investigate a wide range of time scales of molecular motions and to characterize the perturbed lipid dynamics in spatial and temporal depth.