Bacterial cell membrane models: choosing the lipid composition

Alexandra L. Martin, Philip N. Jemmett, Thomas Howitt, Mary H. Wood, Liam R. Cox, Timothy R. Dafforn, Mario Campana, Rebecca J.L. Welbourn, Maximilian W.A. Skoda, Luke A. Clifton, Hadeel Hussain, Jonathan L. Rawle, Francesco Carlà, Christopher L. Nicklin, Thomas Arnold, Sarah L. Horswell

Research output: Contribution to journalArticlepeer-review

Abstract

The reasons for the wide diversity of lipids found in natural cell membranes are still not fully understood but could potentially be exploited in treating disease and infection. This study aims to establish whether charge alone or specific chemical structure of an anionic lipid headgroup determines the structure and properties of model bacterial cell membranes. We compare different compositions of a zwitterionic lipid di-myristoyl phosphatidylethanolamine (DMPE) and two anionic lipids, di-myristoyl phosphatidylglycerol (DMPG) and tetra-myristoyl cardiolipin (TMCL). TMCL has a distinct condensing effect, increasing packing and decreasing the pressures of the phase transitions. Although relatively well solvated itself, TMCL does not substantially alter the solvation of mixed monolayers or bilayers. DMPE:TMCL mixtures have very similar electrochemical behaviour to mixtures of DMPE with di-myristoyl phosphatidylserine (DMPS) but DMPE:DMPG bilayers have greater surface charges. A ternary mixture representing an Escherichia coli membrane has similar electrochemical response to but is more tightly packed than DMPE:DMPG. These results establish the importance of the anionic lipid in modelling different types of cell membranes: DMPG will be required in model bacterial membranes and should not be replaced with DMPS. Even very small amounts of CL will have a measurable effect on structure, so its inclusion is important. Our results also highlight the importance of diverse techniques in understanding membrane behaviour: reflectivity measurements of monolayers over a range of surface pressure provide excellent insight into the electrochemical responses of lipid bilayers, while surface diffraction and infrared spectroscopy are much more sensitive to differences in packing between lipids.

Original languageEnglish
Pages (from-to)7054-7073
Number of pages20
JournalSoft Matter
Volume21
Issue number36
DOIs
StatePublished - Sep 18 2025

Funding

ALM, PNJ and TH gratefully acknowledge the BBSRC-funded Midlands Integrative Biosciences Training Partnerships (BB/M01116X/1, BB/J014532/1 and BB/T00746X/1, respectively) and the University of Birmingham for studentships. We are grateful for the support of Diamond Light Source (experiments SI-22078), the Birmingham-Diamond collaboration (experiment SI-21088) and the Science and Technology Facilities Council (STFC) for access to neutron beamtime and facilities at ISIS Neutron and Muon Source (experiment RB1900125).

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