It is generally believed that antimicrobial peptides, AMPs, are able to evade much of the bacterial resistance because they disturb the fundamental integrity of the entire cell by interfering with the life-defining cell membrane. However, there is no clear general consensus for the molecular basis by which AMPs act, although various structural modifications such as membrane deformation or pore formation have been suggested. [1,2]
In this project we systematically aim to understand the effect of AMP on lipid membranes focusing on both the structure and dynamics. By taking a representative selection of natural AMPs we systemically investigate structural effects on the lipid membrane, the mode of peptide insertion and specifically, whether transmembrane “pores” are formed. To this end we use small-angle X-ray and neutron scattering (SAXS/SANS) in combination with quantitative modelling and auxiliary techniques such as differential scanning calorimetry (DSC).
To investigate the dynamics, more specifically lipid flip-flop and intermembrane diffusion processes, we employ time-resolved SANS and a H/D contrast variation scheme. The results further show that although the structure of the peptide within the membrane differs, all AMPs cause a markedly faster lipid dynamics. [5,6] By using various lipid mixtures and partial H/Dl labelling we show that this effect extend to various lipids (PC, PG, PE)[6,7]. Interestingly, by analysing the temperature dependent rate constants, we show that the acceleration of flip-flop dynamics is not necessarily of enthalpic origin but rather entropic. We will discuss the mechanism in light of recent computer simulation techniques
 H. Jenssen, P. Hamill and R. E. W. Hancock, Clinical Microbiology Reviews, 2006, 19, 491–511.
 W. C., Wimley, ACS Chemical biology 2010, 5 (10), 905-917.
[3 ] J.E. Nielsen, J. E., V:A. Bjørnestad, & R. Lund, Soft Matter, 2018, 11, 37–14.
 Nielsen, J. E., Lind, T. K., Lone, A., Gerelli, Y., Hansen, P. R., Jenssen, H. M, Cárdenas and R. Lund BBA - Biomembranes, 1861(7), 1355–1364.
 Nielsen, J. E.; Bjørnestad, V. A.; Pipich, V.; Jenssen, H.; Lund, R. J. Coll. Int. Sci. 2021, 582, 793–802.
[6 ] Nielsen, J. E.; Prevost, S.; Lund, R. Faraday Discuss., 2021, 232, 203.
[7 ] Nielsen, J. E. and Lund, R. Langmuir, 2022, 38, 374−384.
Dr. Jitae Park
Dr. Theresia Heiden-Hecht
Dr. Dominic Hayward